atrial-natriuretic-factor and Hypotension

The recent development of genetic mouse models presenting life-long alterations in expression of the genes for atrial natriuretic peptide (ANP) or its receptors (NPR-A, NPR-C) has uncovered a physiological role of this hormone in chronic blood pressure homeostasis. Transgenic mice overexpressing a transthyretin-ANP fusion gene are hypotensive relative to the nontransgenic littermates, whereas mice harboring functional disruptions of the ANP or NPR-A genes are hypertensive compared with their respective wild-type counterparts. The chronic hypotensive action of ANP is determined by vasodilation of the resistance vasculature, which is probably mediated by attenuation of vascular sympathetic tone at one or several prejunctional sites. Under conditions of normal dietary salt consumption, the hypotensive action of ANP is dissociated from the natriuretic activity of the hormone. However, during elevated dietary salt intake, ANP-mediated antagonism of the renin-angiotensin system is essential for maintenance of blood pressure constancy, inasmuch as the ANP gene "knockout" mice (ANP -/-) develop a salt-sensitive component of hypertension in association with failure to adequately downregulate plasma renin activity. These findings imply that genetic deficiencies in ANP or natriuretic receptor activity may be underlying causative factors in the etiology of salt-sensitive variants of hypertensive disease and other sodium-retaining disorders, such as congestive heart failure and cirrhosis.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Disease Models, Animal; Hypertension; Hypotension; Mice; Mice, Knockout; Mice, Transgenic; Phenotype; Renin-Angiotensin System; Sodium Chloride; Vasodilation; Water-Electrolyte Balance

Atrial natriuretic factor (ANF) is a peptide hormone that induces potent but transient hypotensive and natriuretic responses on short-term administration. The role of the hormone in long-term cardiovascular regulation has remained elusive in part because of the temporal limitations of long-term infusion models and the extremely short half-life of the molecule in vivo. To circumvent these temporal limitations, a transgenic mouse model was developed that exhibits lifelong elevated plasma ANF levels. These mice are chronically hypotensive, with arterial pressures averaging 20 to 30 mm Hg less than those observed in nontransgenic siblings. In contrast, no obvious natriuretic or diuretic phenotype was observed in transgenic animals housed in metabolic cages. Thus, the mice adequately compensate for the renal effects but not the hemodynamic effects of the hormone. The ANF transgenic mice provide a tractable model system with which to study the consequences of long-term alterations of ANF expression in vivo.

Topics: Animals; Atrial Natriuretic Factor; Hypotension; Mice; Mice, Transgenic; Molecular Biology; Phenotype; Time Factors

Topics: Atrial Natriuretic Factor; Blood Pressure; Humans; Hypertension; Hypotension; Kidney Failure, Chronic; Renal Dialysis

In patients with acute heart failure, early intervention with an intravenous vasodilator has been proposed as a therapeutic goal to reduce cardiac-wall stress and, potentially, myocardial injury, thereby favorably affecting patients' long-term prognosis.. In this double-blind trial, we randomly assigned 2157 patients with acute heart failure to receive a continuous intravenous infusion of either ularitide at a dose of 15 ng per kilogram of body weight per minute or matching placebo for 48 hours, in addition to accepted therapy. Treatment was initiated a median of 6 hours after the initial clinical evaluation. The coprimary outcomes were death from cardiovascular causes during a median follow-up of 15 months and a hierarchical composite end point that evaluated the initial 48-hour clinical course.. Death from cardiovascular causes occurred in 236 patients in the ularitide group and 225 patients in the placebo group (21.7% vs. 21.0%; hazard ratio, 1.03; 96% confidence interval, 0.85 to 1.25; P=0.75). In the intention-to-treat analysis, there was no significant between-group difference with respect to the hierarchical composite outcome. The ularitide group had greater reductions in systolic blood pressure and in levels of N-terminal pro-brain natriuretic peptide than the placebo group. However, changes in cardiac troponin T levels during the infusion did not differ between the two groups in the 55% of patients with paired data.. In patients with acute heart failure, ularitide exerted favorable physiological effects (without affecting cardiac troponin levels), but short-term treatment did not affect a clinical composite end point or reduce long-term cardiovascular mortality. (Funded by Cardiorentis; TRUE-AHF ClinicalTrials.gov number, NCT01661634 .).

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Cardiovascular Diseases; Diuretics; Double-Blind Method; Female; Follow-Up Studies; Heart Failure; Humans; Hypotension; Infusions, Intravenous; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Troponin T

Diuresis is a major therapy for the reduction of congestive symptoms in acute decompensated heart failure (ADHF) patients. Carperitide has natriuretic and vasodilatory effects, and tolvaptan produces water excretion without electrolyte excretion. We previously reported the usefulness of tolvaptan compared to carperitide in ADHF patients with fluid volume retention. The purpose of this study was to examine whether the efficacy of tolvaptan was altered in ADHF patients with reduced left ventricular systolic function and in those with hypotension. A total of 109 hospitalized ADHF patients were randomly assigned to either a tolvaptan or a carperitide treatment group. Baseline clinical characteristics were not different between the two groups. We divided these patients based on the left ventricular ejection fraction (EF) by echocardiography, and blood pressure (BP) at the time of admission. Daily urine volume between the tolvaptan and carperitide groups in patients with preserved EF (≥ 50%) was not different, however, in those with reduced EF (< 50%), the urine volume was significantly higher in the tolvaptan group than in the carperitide group (day 2, 3, 4, P < 0.05 for all). Daily urine volume did not differ between these two groups in the high blood pressure group (BP ≥ 140 mmHg), but was significantly higher in the tolvaptan group than in the carperitide group (day 1, P = 0.021; day 3, P = 0.017) in the low blood pressure group (BP < 140 mmHg). The present study reveals that tolvaptan is more effective than carperitide, especially in ADHF patients with reduced left ventricular systolic function and without hypertension.

Topics: Aged; Aged, 80 and over; Antidiuretic Hormone Receptor Antagonists; Atrial Natriuretic Factor; Benzazepines; Female; Heart Failure; Humans; Hypotension; Male; Middle Aged; Stroke Volume; Tolvaptan; Treatment Outcome; Ventricular Dysfunction, Left

Short daily hemodialysis (HD) has a protective effect against dialysis-induced hypotension (DIH). We examined whether this effect extends beyond the treatment period.. We analyzed clinical variables in 6 patients (5 with diabetes mellitus) who underwent conventional hemodialysis (CHD) for 4 h three times weekly for 12 weeks; then short daily HD for 2 h six times weekly for 12 weeks, and then 12 more weeks of CHD. All patients had been given vasopressors for severe DIH.. The severe DIH disappeared during the short daily HD. There were significant decreases in body weight (BW), cardiothoracic ratio (CTR), blood pressure (BP), normal saline solution (NSS) amount (62.8 +/- 26.4 vs. 9.8 +/- 7.4 ml/session, p < 0.05), frequency (0.60 +/- 0.26 vs. 0.10 +/- 0.07 infusions/session, p < 0.05) and postdialysis atrial natriuretic peptide (ANP) (176.8 +/- 56.4 vs. 104.8 +/- 42.3 pg/ml, p < 0.05). Weekly ultrafiltration volume (6.3 +/- 0.9 vs. 7.9 +/- 0.7 l, p < 0.05) was significantly higher during the short daily HD period than during the first CHD period. The vasopressor treatment was therefore stopped or reduced in all patients during the short daily HD period. Because DIH recurred in the second CHD period despite a significant increase in BP, the vasopressor treatment was resumed in 5 patients. BW, CTR, NSS infusion amount and frequency, or postdialysis ANP did not differ significantly between the short daily HD and second CHD periods.. The protective effect of short daily HD against DIH lasted more than 12 weeks after the treatment ended. We therefore conclude that temporary short daily HD is useful for preventing DIH.

Topics: Aged; Anemia; Antihypertensive Agents; Appointments and Schedules; Arteriovenous Shunt, Surgical; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Diabetic Nephropathies; Echocardiography; Erythropoietin; Female; Ferritins; Humans; Hypertension, Renal; Hypotension; Iron; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Quality of Life; Recombinant Proteins; Renal Dialysis; Uremia

Efficacy and safety assessments for carperitide (alpha-human atrial natriuretic peptide) in previous clinical trials have not mentioned its limitations in practice as therapy for acute heart failure.. A 6-year prospective open-label registry analysis was conducted in the 'real world' of therapy for 3,777 patients with acute heart failure (male 57%, median age 73) treated with 0.085 microg . kg(-1) . min(-1) (median, interquartile 0.05-0.1) of carperitide for 65 h (median, interquartile 22-142); 51% were assessed as class III or IV according to the Killip classification; 82% of the patients were assessed as clinically improved after carperitide treatment. The efficacy limitation was related to the underlying disease (acute myocardial infarction), severity of Killip classification (Class IV), and renal function disturbance. The efficacy was significantly higher in patients with decompensated chronic heart failure (ie, cardiomyopathy, valvular diseases, and hypertensive heart disease). Incidence of adverse events was 16.9%, the most frequent being blood pressure lowering (9.5%), which occurred in the first 3 h of infusion, with 96% of patients recovering or improving without specific treatment. Logistic regression analysis revealed that factors predicting mortality (11.4%) during 7 days of follow-up were age, Killip classification, renal function disturbance, low blood pressure and use of vasopressors.. The clinical condition improved in 82% of patients treated with carperitide. Based on these findings, minute strategy will be established for carperitide therapy within the strata of patient characteristics that may predict the prognosis.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Female; Heart Failure; Humans; Hypotension; Kidney Diseases; Male; Middle Aged; Myocardial Infarction; Prognosis; Regression Analysis; Risk Factors; Severity of Illness Index; Treatment Outcome; Vasoconstrictor Agents

We evaluated the effects of moderate colloid preloading on hemodynamics and plasma concentration of atrial natriuretic peptide (ANP) during spinal anesthesia in elderly patients undergoing low extremity surgery. Twenty patients (aged 66-90 yr) were randomly divided into two groups. Control group (n = 10) received no prehydration, and hydration group (n = 10) received colloid (6% hydroxyethyl starch; HES) preloading of 8 ml.kg-1 before spinal anesthesia. Systolic blood pressure decreased significantly 10 and 30 min after spinal anesthesia in either group, and there was no difference between the groups in the incidence of hypotension. The concentration of ANP decreased significantly by 23% in control group, whereas it increased significantly by 86% in hydration group, suggesting that cardiac preload might increase with volume expansion effect of prehydration with HES. In conclusion, colloid preloading with moderate volume might prevent the decrease in cardiac preload with increasing ANP, whereas it did not prevent spinal-induced hypotension in elderly patients.

Topics: Aged; Aged, 80 and over; Anesthesia, Spinal; Atrial Natriuretic Factor; Colloids; Female; Hemodynamics; Humans; Hydroxyethyl Starch Derivatives; Hypotension; Male; Preanesthetic Medication

In recent years, the concept of prophylactic volume expansion to prevent hypotension caused by spinal anesthesia has been challenged. Investigators have reevaluated the concept of prehydration in the obstetric patient and the physiologic mechanisms involved. This article addresses whether the hypotensive effects attributed to the atrial natriuretic factor are the reason for the apparent failure of prehydration.. Atrial natriuretic factor was measured before (baseline) and 10 min after spinal anesthetic drug injection (control) in 48 healthy pregnant patients scheduled for elective cesarean section. Sixteen patients received hydration with 15 ml/kg crystalloid immediately before spinal anesthesia, 16 patients received the same volume starting with the spinal anesthetic injection, and the remaining 16 patients received no prehydration (control). Blood pressure, heart rate, ephedrine requirements, infused fluids, and urine output were measured.. Atrial natriuretic factor concentrations increased significantly in prehydrated patients but not in the control group. There was a significant correlation in the change in atrial natriuretic factor concentrations and urine output but no correlation in the control atrial natriuretic factor concentrations and blood pressure or ephedrine requirements. Ephedrine requirements and blood pressure did not differ significantly among study groups.. Atrial natriuretic factor is a potent endogenous diuretic in the pregnant patient but does not appear to be involved in short-term cardiovascular homeostasis after spinal anesthesia. Prehydration appears to be an ineffective measure to prevent post spinal hypotension in the obstetric patient [corrected].

Topics: Adult; Anesthesia, Obstetrical; Anesthesia, Spinal; Atrial Natriuretic Factor; Ephedrine; Female; Hemodynamics; Humans; Hypotension; Pregnancy; Vasoconstrictor Agents

Intravenous infusion of nesiritide, a brain (B-type) natriuretic peptide, has beneficial hemodynamic effects in patients with decompensated congestive heart failure. We investigated the clinical use of nesiritide in such patients.. Patients hospitalized because of symptomatic congestive heart failure were enrolled in either an efficacy trial or a comparative trial. In the efficacy trial, which required the placement of a Swan-Ganz catheter, 127 patients with a pulmonary-capillary wedge pressure of 18 mm Hg or higher and a cardiac index of 2.7 liters per minute per square meter of body-surface area or less were randomly assigned to double-blind treatment with placebo or nesiritide (infused at a rate of 0.015 or 0.030 microg per kilogram of body weight per minute) for six hours. In the comparative trial, which did not require hemodynamic monitoring, 305 patients were randomly assigned to open-label therapy with standard agents or nesiritide for up to seven days.. In the efficacy trial, at six hours, nesiritide infusion at rates of 0.015 and 0.030 microg per kilogram per minute decreased pulmonary-capillary wedge pressure by 6.0 and 9.6 mm Hg, respectively (as compared with an increase of 2.0 mm Hg with placebo, P<0.001), resulted in improvements in global clinical status in 60 percent and 67 percent of the patients (as compared with 14 percent of those receiving placebo, P<0.001), reduced dyspnea in 57 percent and 53 percent of the patients (as compared with 12 percent of those receiving placebo, P<0.001), and reduced fatigue in 32 percent and 38 percent of the patients (as compared with 5 percent of those receiving placebo, P<0.001). In the comparative trial, the improvements in global clinical status, dyspnea, and fatigue were sustained with nesiritide therapy for up to seven days and were similar to those observed with standard intravenous therapy for heart failure. The most common side effect was dose-related hypotension, which was usually asymptomatic.. In patients hospitalized with decompensated congestive heart failure, nesiritide improves hemodynamic function and clinical status. Nesiritide is useful for the treatment of decompensated congestive heart failure.

Topics: Atrial Natriuretic Factor; Cardiotonic Agents; Dose-Response Relationship, Drug; Double-Blind Method; Dyspnea; Fatigue; Female; Heart Failure; Humans; Hypotension; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Wedge Pressure; Vasodilator Agents

Our purposes were (1) to examine resting arterial blood pressure following an acute bout of resistance exercise and submaximal dynamic exercise, (2) to examine the effects of these exercises on the plasma concentrations of atrial natriuretic peptide ([ANP]), and (3) to evaluate the potential relationship between [ANP] and post-exercise blood pressure. Thirteen males [24.3+/-(2.4) years] performed 15 min of unilateral leg press exercise (65% of their one-repetition maximum) and, I week later, approximately 15 min of cycle ergometry (at 65% of their maximum oxygen consumption). Intra-arterial pressure was monitored during exercise and for 1 h post-exercise. Arterial blood was drawn at rest, during exercise and at intervals up to 60 min post-exercise for analysis of haematocrit and [alphaANP]. No differences occurred in blood pressure between trials, but significant decrements occurred following exercise in both trials. Systolic pressure was approximately 20 mmHg lower than before exercise after 10 min, and mean pressure was approximately 7 mmHg lower from 30 min onwards. Only slight (non-significant) elevations in [alphaANP] were detected immediately following exercise, with the concentrations declining to pre-exercise values by 5 min post-exercise. We conclude that post-exercise hypotension occurs following acute bouts of either resistance or submaximal dynamic exercise and, in this investigation, that this decreased blood pressure was not directly related to the release of alphaANP.

Topics: Adult; Atrial Natriuretic Factor; Bicycling; Blood Pressure; Exercise; Heart Rate; Hematocrit; Humans; Hypotension; Male; Oxygen Consumption; Time Factors

Ularitide is a member of the natriuretic peptide family. This hormone exhibits an N-terminal extension by four amino acids compared with atrial natriuretic peptide. Ularitide was shown to exert strong diuretic and natriuretic effects when infused intravenously. Its main action sites are the glomerulum, inducing preglomerular vasodilation and postglomerular vasoconstriction and thereby elevating the glomerular filtration rate, and the tubular system inhibiting Na(+)-reabsorption. In initial uncontrolled clinical trials, this peptide was shown to have beneficial effects in patients suffering from oliguric acute renal failure.. We conducted a double-blind, placebo-controlled, multicenter, dose-finding trial recruiting 176 patients randomized into 4 different Ularitide doses groups (U5, U20, U40, and U80 ng/kg/min) and a placebo group (U0). Ularitide/placebo infusion was performed for 5 days with half the originally infused dose on day 5. The primary objective of the study was to test various doses of Ularitide in patients suffering from oliguric acute renal failure to avoid mechanical renal replacement therapy during the first 12 hours.. The results indicate that Ularitide does not reduce the incidence of mechanical renal replacement therapy compared with placebo-treated patients during the first 12 h of treatment (U0: 36 (20), U5: 35 (11), U20: 36 (9), U40: 28 (8), U80: 41 (12), (% (n) (p = 0.87)). Diuresis increased in the Ularitide-treated groups and the placebo group after onset of infusion and did not show any significant difference in the first 12 h collection period (U0: 576, U5: 514, U20: 500, U40: 360, U80: 158 ML/12h (Median), (p = 0.16)).. In summary, the incidence of mechanical renal replacement therapy in critically ill patients suffering from oliguric acute renal failure could not be altered positively by Ularitide administration according to our protocol. Further prospective clinical trials are needed to answer the question whether a different patient collective or a prophylactic administration of Ularitide are more promising approaches in the clinical setting of oliguric acute renal failure.

Topics: Acute Kidney Injury; Aged; Atrial Natriuretic Factor; Blood Pressure; Blood Urea Nitrogen; Cardiovascular Diseases; Creatinine; Diuretics; Double-Blind Method; Female; Humans; Hypotension; Male; Middle Aged; Peptide Fragments; Renal Replacement Therapy; Time Factors

The endogenous release of the vasoactive peptides atrial natriuretic peptide and endothelin-1 may modify maternal haemodynamic responses to a rapid intravenous volume load used to prevent hypotension at elective Caesarean delivery under spinal anaesthesia. Twenty-two healthy pregnant women were examined during elective Caesarean section at term pregnancy. They were randomly assigned to receive either 2000 ml of Ringer lactate solution (crystalloid group) or 500 ml of 6% hydroxyethyl starch + 1000 ml of Ringer lactate solution (colloid group). The mean (SEM) concentration of atrial natriuretic peptide in plasma increased from 10.9 (1.5) to 24.7 (5.1) pmol.l-1 during crystalloid infusion and from 10.3 (1.4) to 28.2 (5.6) pmol.l-1 during colloid infusion. A slight decrease in endothelin-1 levels was found during colloid infusion. A significant increase in the release of atrial natriuretic peptide in response to volume load may decrease vascular tone and initiate diuresis, thereby attenuating the effect of volume load on blood pressure during elective Caesarean delivery.

Topics: Adult; Anesthesia, Obstetrical; Anesthesia, Spinal; Atrial Natriuretic Factor; Cesarean Section; Endothelins; Female; Fluid Therapy; Hemodynamics; Humans; Hydroxyethyl Starch Derivatives; Hypotension; Isotonic Solutions; Pregnancy; Preoperative Care; Ringer's Lactate

In this pilot study we investigated the effects of a 4-h infusion of atrial natriuretic peptide (8-33 Met ANP) on hemodynamic, renal, and hormonal parameters in 12 patients with hypertension. Either 8-33 ANP in 5% mannitol (0.7 microgram/min [eight patients] and 1.05 micrograms/min [four patients]) or placebo (5% mannitol) was infused for 4 h on 2 consecutive days in a randomized double-blind crossover design. The plasma levels of ANP were not significantly different between the two doses of ANP and therefore the results from the two doses were combined. Plasma ANP increased from 61 +/- 24 pg/mL to 291 +/- 55 pg/mL after 2 h and to 288 +/- 40 pg/mL after 4 h. ANP caused a significant lowering of systolic blood pressure after 2 h of infusion from 148 +/- 5 mm Hg to 142 +/- 5 mm Hg (P less than .05) and to 128 +/- 6 after 4 h (P less than .01). Two hours after discontinuation of the infusion, systolic blood pressure was 126 +/- 6 and 135 +/- 7 mm Hg 4 h after the end of the infusion. Diastolic blood pressure did not change. Heart rate increased from 69 +/- 3 beats/min to 74 +/- 3 beats/min after 4 h and to 78 +/- 4 beats/min 2 h after termination of the infusion. Cardiac output did not change significantly. Urinary sodium and chloride increased significantly but creatinine clearance did not change. Plasma aldosterone decreased after 2 h of ANP infusion from 9.8 +/- 1.7 ng/dL to 6.7 +/- 0.9 ng/dL (P less than .01) and to 6.5 +/- 1.2 ng/dL after 4 h (P less than .05). Plasma renin activity decreased from 0.81 +/- 0.1 ng angiotensin I/mL/h to 0.57 +/- 0.1 after 2 h of infusion (P less than .05). There were no significant changes in plasma catecholamines or arginine vasopressin. Two patients developed severe hypotension and bradycardia and one of them had a sinus pause of 7.4 sec associated with loss of consciousness. Neither of these two patients had a significant increase in plasma catecholamines in response to the severe hypotension, suggesting that ANP may have inhibited their sympathetic response and increased their sensitivity to vagal cardioinhibitory reflexes. In conclusion, infusion of ANP in hypertensive patients causes prolonged lowering of systolic blood pressure with no change in diastolic pressure and cardiac output.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Bradycardia; Diuresis; Double-Blind Method; Female; Heart Rate; Humans; Hypertension; Hypotension; Infusions, Intravenous; Male; Middle Aged; Renin

We sought to demonstrate a hypotensive effect from infusions of atrial natriuretic factor (ANF) into humans and to describe the mechanism(s) of this effect. Cardiovascular and hormonal responses to human ANF-(99-126) (125 ng/kg bolus followed by a 30-minute infusion at 25 ng/kg/min) were determined in eight conscious volunteers and compared with responses of eight time-control subjects who received isotonic saline. Baseline levels of ANF (52.8 +/- 5.5 pg/ml) increased 8.8-fold after 30 minutes of ANF infusion but were unchanged in the time controls. Plasma levels of renin, aldosterone, vasopressin, sodium, potassium, and osmolality did not change during infusions. A transient 5% reduction in mean arterial pressure related to a 12% reduction in peripheral resistance was observed 10 minutes after the priming bolus of ANF. This response was not sustained during the remainder of the ANF infusion period, nor did it occur in two additional subjects who received ANF infusions without the priming bolus. Steady state responses consisted of significant reductions in central venous pressure (15%), stroke volume (13%), and cardiac output (10%), but no reduction in blood pressure. Plasma norepinephrine levels and peripheral resistance increased (34% and 9%, respectively) during ANF administration. These data indicate that steady state responses to ANF in humans consist of decreases in cardiac filling pressures, which reduce cardiac output, unload cardiopulmonary baroreceptors, and activate the sympathetic nervous system. Blood pressure is well maintained despite striking increases in plasma ANF.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Cardiac Output; Central Venous Pressure; Forearm; Hemodynamics; Homeostasis; Hormones; Humans; Hypotension; Infusions, Intravenous; Injections, Intravenous; Norepinephrine; Sympathetic Nervous System; Time Factors; Vascular Resistance

Synthetic atrial natriuretic factor (ANF) was administered in ascending doses (0.03, 0.20, 0.45 microgram/kg/min) to eight mildly essential hypertensive men on high (200 mEq/day) or low (10 mEq/day) sodium diets. Responses of blood pressure, heart rate, urinary volume and electrolyte excretion, renin, and aldosterone were measured. For the entire group, ANF lowered blood pressure and increased heart rate during the 0.20 and 0.45 microgram/kg/min infusions, and the antihypertensive effect of the peptide persisted for at least 2 hours after the infusions ended. Four patients (2 at 0.20 microgram/kg/min and 2 at 0.45 microgram/kg/min) experienced sudden bradycardia and hypotension at the end of or shortly after completion of ANF infusion. Renal excretion of water, sodium, chloride, calcium, and phosphorus increased in a dose-dependent fashion in response to infused ANF. Patients on the 200 mEq/day sodium diet had greater increases in urinary volume (11.1 +/- 2.8 vs 3.0 +/- 2.0 ml/min; p less than 0.05), sodium (870 +/- 134 vs 303 +/- 27 microEq/min; p less than 0.05), and chloride (801 +/- 135 vs 176 +/- 75 microEq/min; p less than 0.02) compared with patients on the low sodium diet. The apparent direct suppressive effect of a 0.03 microgram/kg/min infusion of ANF on renin and aldosterone levels was overcome at higher doses by counterregulation provoked by the depressor action. Renin was slightly (-12%) suppressed during the 0.03 microgram/kg/min infusion of ANF but increased at the 0.20 (+50%) and 0.45 microgram/kg/min (+90%; p less than 0.03) rates. Aldosterone declined significantly during the 0.03 microgram/kg/min infusion (-45%; p less than 0.01) of ANF but not during the two higher dose infusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Diuretics; Dose-Response Relationship, Drug; Heart Rate; Hormones; Humans; Hypertension; Hypotension; Male; Middle Aged; Peptide Fragments; Renin-Angiotensin System; Sodium Chloride; Water-Electrolyte Balance

Sacubitril/valsartan (S/V) treatment is beneficial in patients with heart failure with reduced ejection fraction (HFrEF), but its mode of action remains elusive, although it involves the increase in ANP (atrial natriuretic peptide).. Combining mass spectrometry and enzymatic assay in the plasma of 73 HFrEF patients treated with S/V and controls, we deciphered proANP processing that converts proANP into 4 vasoactive peptides.. We found that proANP processing is sequential and involved meprin B, ECE (endothelin-converting enzyme) 1, and ANPEP (aminopeptidase N). This processing is limited in HFrEF patients via the downregulation of proANP production, corin, and meprin B activities by miR-425 and miR1-3p. S/V restored or compensated proANP processing by downregulating miR-425 and miR1-3p, hence increasing levels of proANP-derived bioactive peptides. In contrast, S/V directly and indirectly partially inhibited ECE1 and ANPEP. ECE1 partial inhibition resulted in a lower-than-expected increase in ET1 (endothelin 1), tilting the vasoactive balance toward vasodilation, and possibly hypotension. Furthermore, proANP glycosylation interferes with the midregional proANP assay -a clinical surrogate for proANP production, preventing any pathophysiological interpretation of the results. The analysis of S/V dose escalation with respect to baseline treatments suggests S/V-specific effects.. These findings offer mechanistic evidence to the natriuretic peptide -defective state in HFrEF, which is improved by S/V. These data also strongly suggests that S/V increases plasma ANP by multiple mechanisms that involve 2 microRNAs, besides its protection from NEP (neprilysin) cleavage. Altogether, these data provide new insights on HFrEF pathophysiology and the mode of action of S/V.

Topics: Aminobutyrates; Atrial Natriuretic Factor; Biphenyl Compounds; Drug Combinations; Heart Failure; Humans; Hypotension; MicroRNAs; Neprilysin; Stroke Volume; Valsartan

Human atrial natriuretic peptide, known as carperitide, is approved for early relief of dyspnea in patients with acute heart failure (AHF). However, the diuretic effect of carperitide is sometimes insufficient for controlling volume overload. We investigated predictors for the carperitide response in patients with AHF. Forty-seven patients (age: 74 ± 10 years; left ventricular ejection fraction: 42.0% ± 15.9%) with AHF were enrolled and treated with carperitide monotherapy at a dose of 0.0125 μg/kg/min. Patients without sufficient diuresis (< 60 ml/h) or improvement of symptoms by 4 h after carperitide administration, despite increasing to twice the dose of carperitide and adding another agent, were defined as non-responders. Twenty-four (51%) patients were defined as responders and treated with low-dose carperitide monotherapy on the first day. Multiple logistic regression analysis showed that the response to carperitide monotherapy was independently predicted by serum creatinine levels and systolic blood pressure (SBP) on admission. The area under the receiver-operating characteristic curve for predicting the response to carperitide by SBP was 0.808 (95% confidence interval [0.686-0.930], sensitivity: 83.3%, specificity: 65.2%, cutoff value: 135 mmHg). Four (8.5%) patients developed asymptomatic transient hypotension. Worsening renal function occurred within 3 days of admission in three (6.4%) patients who received low-dose carperitide therapy. SBP and serum creatinine levels on admission might be useful for predicting the diuretic response to low-dose carperitide monotherapy in patients with AHF. Initial use of low-dose carperitide therapy does not have adverse effects on renal function.

Topics: Acute Disease; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Creatinine; Diuresis; Diuretics; Dyspnea; Female; Heart Failure; Humans; Hypotension; Male; Middle Aged; Predictive Value of Tests; Recovery of Function; Retrospective Studies; Time Factors; Treatment Outcome

Topics: Atrial Natriuretic Factor; Humans; Hypotension; Natriuresis; Natriuretic Peptides

Predictors of worsening renal function (WRF: increase in serum creatinine ≥ 0.3 mg/dl from the value on admission) in patients with acute decompensated heart failure (ADHF) treated by low-dose carperitide (0.01-0.05 μg/kg/min) are unclear.. We retrospectively investigated predictors of WRF within the first 24 h of low-dose carperitide therapy in 205 patients (mean age, 75.6 ± 12.1 years) hospitalized for ADHF and treated with low-dose carperitide between January 2006 and April 2014. WRF occurred in 14 patients (7%). A multivariate adjustment analysis showed that independent predictors of WRF within 24 h were hypotension (systolic blood pressure <90 mmHg) within 12 h (odds ratio, 8.7; 95% confidence interval, 2.38-35.88; P=0.0012) and serum creatinine on admission (odds ratio, 3.64; 95% confidence interval, 1.84-7.67; P=0.0003). In patients with estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2), the rate of WRF occurrence was higher in those complicated by hypotension than in those without hypotension (22.6% [7/31 patients] vs. 4.4% [5/113 patients], P=0.0041). In contrast, in patients with eGFR ≥ 60 ml/min/1.73 m(2), hypotension did not influence the occurrence of WRF (0% [0/9 patients] vs. 3.9% [2/51 patients], P=NS).. Hypotension within 12 h and renal dysfunction on admission are independent predictors of WRF within 24 h in patients with ADHF treated by low-dose carperitide. Hypotension may not cause WRF in patients with eGFR ≥ 60 ml/min/1.73 m(2).

Topics: Acute Disease; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Creatinine; Female; Glomerular Filtration Rate; Heart Failure; Humans; Hypotension; Kidney Diseases; Male; Middle Aged; Retrospective Studies

Fluid bolus administration is a standard treatment for hypotension. However, the effectiveness of the traditional prophylactic bolus in parturients undergoing spinal anesthesia for cesarean delivery has been questioned. One potential mechanism for the failure of a prophylactic fluid bolus to prevent hypotension is hypervolemia-induced destruction of the endothelial glycocalyx, a structure that plays a vital role in regulating intravascular fluid shifts.. Thirty healthy parturients undergoing elective cesarean delivery under spinal anesthesia were recruited. Known endothelial glycocalyx biomarkers, heparan sulfate and syndecan-1 along with atrial natriuretic peptide, were measured before and after a 750-mL crystalloid fluid bolus. Cardiac performance parameters, cardiac index and systemic vascular resistance, were monitored during the fluid bolus using thoracic-impedance cardiography.. A significant increase in both heparan sulfate 96 ng/mg (P=0.0098) and syndecan-1 2.4 ng/mg (P=0.045) were observed after the fluid bolus. There was a non-significant increase in atrial natriuretic peptide 0.6 pg/mg (P=0.293). Cardiac parameters showed a small but significant change; over an average of 15 min, cardiac index increased by 0.1L/min/m2 (P=0.0005) and systemic vascular resistance decreased by 30.7 dyn.s/cm5 (P=0.0025).. A prophylactic fluid bolus in parturients undergoing spinal anesthesia for cesarean delivery disrupts the endothelial glycocalyx, as noted by a statistically significant increase in post-bolus heparan sulfate and syndecan-1 levels. Although studied in the past, atrial natriuretic peptide could not explain this disruption. Our fluid bolus did not have a clinically relevant effect on cardiac performance.

Topics: Adult; Anesthesia, Obstetrical; Anesthesia, Spinal; Atrial Natriuretic Factor; Cesarean Section; Endothelium, Vascular; Female; Fluid Therapy; Glycocalyx; Heparitin Sulfate; Humans; Hypotension; Pregnancy; Prospective Studies; Syndecan-1

The natriuretic/diuretic response to atrial natriuretic peptide (ANP), an important regulator of water and Na(+) balance, is markedly attenuated in nephrotic syndrome (NS). It has been suggested that the diminished renal responsiveness to ANP may contribute to the pathogenesis of salt retention and edema formation in NS. However, the mechanisms underlying the renal hyporesponsiveness to ANP remain largely unknown.. The acute effects of exogenous infusion of ANP (5 µg/kg + 10 µg/kg/h) were studied by clearance methodology in control rats, hypoalbuminemic rats with Adriamycin (ADR)-induced NS and in ADR-treated rats infused with hyperoncotic albumin sufficient to restore plasma albumin to normal levels.. Administration of ANP to control rats resulted in a significant increase in urinary flow rate, absolute rate of sodium excretion (+456%) and glomerular filtration rate (GFR). Mean arterial blood pressure decreased following infusion of the peptide. In the nephrotic rats, baseline GFR and Na(+) excretion were significantly lower than in the control animals, and the renal effects of ANP were markedly blunt compared to the control animals. In contrast, the hypotensive effect of ANP in the ADR-treated rats was largely preserved. Infusion of hyperoncotic albumin prior to ANP administration reversed the decrease in baseline GFR and Na(+) excretion and completely restored the renal effects of ANP in the nephrotic rats.. These findings indicate that renal hyporesponsiveness to ANP in rats with ADR-induced NS is a reversible phenomenon that appears to be of functional origin rather than reflecting permanent cellular damage.

Topics: Albumins; Animals; Atrial Natriuretic Factor; Blood Pressure; Disease Models, Animal; Doxorubicin; Edema; Glomerular Filtration Rate; Humans; Hypotension; Inulin; Kidney; Male; Natriuresis; Nephrosis; Nephrotic Syndrome; Rats; Rats, Sprague-Dawley; Renal Circulation; Renin; Salts; Sodium

A-type (atrial) natriuretic peptide (ANP) levels in the heart and plasma were examined by immunohistochemistry, electron microscopy, and radioimmunoassay (RIA) in angiotensin II type 1a receptor knockout (Agtr1a KO) mice. Additionally, the ANP mRNA level in the heart was measured using a real-time polymerase chain reaction (PCR) assay. The blood pressure in Agtr1a KO mice was significantly lower than that in wild-type (WT) mice. The number of ANP granules and ANP immunoreactivity in the auricular cardiocytes were significantly lower in Agtr1a KO mice than in WT mice. Ultrastructurally, the ventricular cardiocytes in Agtr1a KO mice occasionally had ANP-like granules, which were not present in WT mice. The plasma, auricular, and ventricular ANP and plasma cyclic guanosine monophosphate (cGMP) concentrations were significantly higher in Agtr1a KO mice than in WT mice. The ANP mRNA levels of the auricular and ventricular cardiocytes in the Agtr1a KO mice were almost twice as large as those in WT mice. The present data suggest that a notable increase in the ANP biosynthesis and release in the heart of Agtr1a KO mice may account for the reduction in blood pressure together with the lack of an AGTR1A receptor in this model.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Disease Models, Animal; Gene Expression; Heart Atria; Heart Ventricles; Hypotension; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardium; Myocytes, Cardiac; Receptor, Angiotensin, Type 1; RNA, Messenger

Extremely low birth weight infants (ELBWI) often suffer from severe hypotension in the early neonatal period. However, few previous studies have ever revealed plasma levels of vasoactive substances which regulate the cardiovascular system in ELBWI.. To study plasma levels of vasoactive substances in ELBWI with hypotension during the first 24 h of life.. 22 ELBWI with hypotension (gestational age 26.4 +/- 1.9 weeks; birth weight 751 +/- 135 g) were involved in the study. After initial volume therapy, the infants were arbitrarily divided into two groups depending on requirement of dopamine dosage: severe hypotension group (SH; dopamine >10 microg/kg/min, n = 9) and mild hypotension group (MH; dopamine

Topics: Arginine Vasopressin; Atrial Natriuretic Factor; Cardiotonic Agents; Catecholamines; Dopamine; Dose-Response Relationship, Drug; Humans; Hypotension; Infant, Extremely Low Birth Weight; Infant, Newborn

In addition to haemodynamic actions, Ucn1 (urocortin 1) has been reported to affect a number of hormonal systems; however, it remains unclear whether Ucn1 modulates circulating hormones under physiological conditions. Accordingly, in the present study, we have examined the effects of Ucn1 on haemodynamics, hormones and renal indices in normal conscious sheep subjected to a nitroprusside-induced hypotensive stimulus designed to alter hormonal levels within the physiological range. Ucn1 administration did not alter the haemodynamic response to nitroprusside-induced hypotension. However, compared with the rise observed on the control day, plasma ANP (atrial natriuretic peptide; P=0.043), BNP (brain natriuretic peptide; P=0.038) and endothelin-1 (P=0.011) levels were reduced following Ucn1 administration. Associated with this significant reduction in natriuretic peptides, the increase in urinary sodium output associated with rising pressures post-nitroprusside was abolished following Ucn1 administration (P=0.048). Ucn1 had no significant effect on the response of hormones of the renin-angiotensin-aldosterone system or the hypothalamo-pituitary-adrenal axis. In conclusion, Ucn1, administered at physiologically relevant levels during nitroprusside-induced hypotension, attenuates the secretion/release of endothelin-1 and the cardiac natriuretic peptides ANP and BNP. Suppression of ANP and BNP probably led to an attenuated natriuretic response to recovery from acute hypotension. The threshold for the action of Ucn1 on the natriuretic peptides and endothelin-1 appears to be below that of other actions of Ucn1.

Topics: Aldosterone; Angiotensin II; Animals; Antihypertensive Agents; Atrial Natriuretic Factor; Blood Pressure; Cardiac Output; Corticotropin-Releasing Hormone; Cyclic GMP; Heart Rate; Hypotension; Natriuretic Peptide, Brain; Nitroprusside; Sheep; Urocortins

The persistent sexual arousal syndrome (PSAS) is a newly described entity where the woman becomes involuntarily genitally aroused for extended periods of time in the absence of sexual desire and is distressed by this situation. The cause of this sexual problem is not well understood. We describe such a case where the subjective feelings were confirmed by observing genital engorgement. In her case, PSAS came on after initiation of fludrocortisone given for hypotension and bradycardia that was associated with an atrial septal defect (ASD). We argue that the combined effect of the ASD and fludrocortisone may be associated with an increase in her levels of atrial natriuretic peptide (ANP). ANP causes profound vasodilation and vascular leakage. We postulate that the high serum levels of ANP in her case may be contributory to her PSAS.

Topics: Anti-Inflammatory Agents; Atrial Natriuretic Factor; Bradycardia; Female; Fludrocortisone; Heart Septal Defects, Atrial; Humans; Hypotension; Middle Aged; Sexual Dysfunctions, Psychological

Sildenafil citrate (Viagra) is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5, which might enhance the vasorelaxant and natriuretic actions of atrial natriuretic peptide (ANP) in patients with heart failure. The objective of this study was to examine the combined effect of Viagra on hemodynamic changes during infusion of exogenous ANP.. Healthy male beagles were used to assess systemic blood pressure, pulmonary artery pressure (PAP), and plasma levels of cGMP. After hemodynamic variables were measured, 0.1 microg.kg(-1).min(-1) of ANP was given during this study. One hour after initiating infusion of ANP, 2 mg/kg of sildenafil citrate or vehicle was given orally via a nasogastric tube. Hemodynamic changes were measured before and 1 h after these administrations. Mean systemic and PAP decreased during infusion of ANP, and further decreased after sildenafil citrate administration, however, mean systemic blood pressure decreased within 10 mmHg. Plasma levels of cGMP also increased after sildenafil citrate administration.. In normal dogs, sildenafil citrate enhances the vasodilator effect of ANP by increasing the cGMP level, however, the concomitant use of sildenafil citrate with ANP will not induce severe hypotension.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Cyclic GMP; Dogs; Drug Synergism; Heart Rate; Hypotension; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vasodilation; Vasodilator Agents

Atrial natriuretic peptide (ANP), via its vasodilating and diuretic effects, has an important physiological role in the maintenance of arterial blood pressure and volume. Its guanylyl cyclase-A (GC-A) receptor is highly expressed in vascular endothelium, but the functional relevance of this is controversial. To dissect the endothelium-mediated actions of ANP in vivo, we inactivated the GC-A gene selectively in endothelial cells by homologous loxP/Tie2-Cre-mediated recombination. Notably, despite full preservation of the direct vasodilating effects of ANP, mice with endothelium-restricted deletion of the GC-A gene (EC GC-A KO) exhibited significant arterial hypertension and cardiac hypertrophy. Echocardiographic and Doppler flow evaluations together with the Evan's blue dilution technique showed that the total plasma volume of EC GC-A KO mice was increased by 11-13%, even under conditions of normal dietary salt intake. Infusion of ANP caused immediate increases in hematocrit in control but not in EC GC-A KO mice, which indicated that ablation of endothelial GC-A completely prevented the acute contraction of intravascular volume produced by ANP. Furthermore, intravenous ANP acutely enhanced the rate of clearance of radio-iodinated albumin from the circulatory system in control but not in EC GC-A KO mice. We conclude that GC-A-mediated increases in endothelial permeability are critically involved in the hypovolemic, hypotensive actions of ANP.

Topics: Animals; Arteries; Atrial Natriuretic Factor; Capillary Permeability; Cardiomegaly; Endothelium, Vascular; Guanylate Cyclase; Hematocrit; Humans; Hypotension; Hypovolemia; Integrases; Mice; Mice, Knockout; Myocytes, Cardiac; Receptors, Atrial Natriuretic Factor; Vasodilation; Viral Proteins

We hypothesized that caloric restriction (CR)-induced hypotension would correlate with increased sodium excretion through an atrial natriuretic peptide (ANP)-dependent mechanism. To test this hypothesis, the cardiovascular parameters of c57/Bl mice were measured with radiotelemetry while urine was collected. The 23-h mean blood pressure (BP) dropped from 108.6 +/- 1.8 to 92.7 +/- 2.4 mmHg, and 23-h heart rate dropped from 624 +/- 5 to 426 +/- 13 beats/min over 7 days of CR at 29 degrees C. Contrary to our hypothesis, urine sodium excretion decreased by 55% by day 7 of CR. Consistent with decreased sodium excretion was the drop in plasma ANP (from 82.4 +/- 4.3 to 68.0 +/- 5.8 pg/ml). To explore the possibility that CR lowers BP through an ANP receptor-dependent mechanism that is independent of its effect on sodium retention, we measured the cardiovascular parameters of mice deficient in the ANP receptor (NPR1(-/-)) or the ANP clearance receptor (NPR3(-/-)). Mean BP fell from 117.1 +/- 3.9 to 108.0 +/- 4.7 mmHg in the NPR1(-/-) mice and from 87.0 +/- 2.4 to 78.4 +/- 1.7 mmHg in the NPR3(-/-) mice during CR. These data indicate that the hypotension induced by CR does not depend on increased sodium excretion. Rather, it appears that the mouse responds to the low BP induced by CR with an increase in sodium reabsorption. Furthermore, circulating ANP levels and data from NPR1(-/-) and NPR3(-/-) mice suggest that the ANP pathway may not be involved in the cardiovascular response to CR.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Bradycardia; Caloric Restriction; Consciousness; Female; Guanylate Cyclase; Heart Rate; Hypotension; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Parasympathetic Nervous System; Receptors, Atrial Natriuretic Factor; Salts; Sympathetic Nervous System; Telemetry; Water-Electrolyte Balance

Hypovolemia is thought to have an important role in the pathogenesis of dialysis-related hypotension.. We studied the effect of hypovolemia simulated by lower body negative pressure (LBNP) in 11 hypotension-prone (HP) and 11 hypotension-resistant (HR) hemodialysis patients. LBNP was applied stepwise from 0 to -20 to -40 mm Hg. Systolic arterial pressure, heart rate, and central venous pressure (CVP) were recorded continuously after cannulation of the right jugular vein. Stroke volume index was measured at each step echocardiographically. At the end of each level of LBNP, blood samples were obtained to measure norepinephrine (NE), epinephrine (E), and atrial natriuretic peptide (ANP) levels.. At baseline, CVP (12 +/- 5 and 16 +/- 7 mm Hg), heart rate (72 +/- 9 and 70 +/- 13 beats/min), cardiac index (2.3 +/- 0.6 and 2.5 +/- 0.9 L/min), NE (median, 341 pg/mL [range,198 to 789 pg/mL] and 365 pg/mL [range, 177 to 675 pg/mL] or 2.02 nmol/L [range, 1.17 to 4.66 nmol/L] and 2.16 nmol/L [range, 1.05 to 4.00 nmol/L]), E (median, 46 pg/mL [range, 18 to 339 pg/mL] and 58 pg/mL [range, 21 to 122 pg/mL] or 251 pmol/L [range, 98 to 1,951 pmol/L] and 317 pmol/L [range, 115 to 666 pmol/L]) were similar, whereas systolic arterial pressure (141 +/- 26 versus 164 +/- 22 mm Hg) and ANP (median, 441 pg/mL [range, 152 to 1,330 pg/mL] versus 804 pg/mL [range, 517 to 3,560 pg/mL] ng/L) were lower (P < 0.05) in HP patients. In response to LBNP (-40 mm Hg), CVP decreased by 6.5 +/- 4.0 mm Hg in the HP group and 4.9 +/- 4.9 mm Hg in the HR group. In HP patients, this decrease was associated with a greater decrease in SI (37% +/- 16% versus 27% +/- 16%) and systolic arterial pressure (19% +/- 21% versus 4% +/- 14%) than in HR patients. Plasma ANP levels did not change, whereas increases in NE and E levels were similar in HP and HR patients.. Patients who frequently experience episodes of hypotension during dialysis also are prone to develop hypotension during LBNP, which results from reduced myocardial contractile reserve and/or inadequate sympathetic tone.

Topics: Aged; Atrial Natriuretic Factor; Cardiac Output, Low; Catecholamines; Disease Susceptibility; Female; Hemodynamics; Humans; Hypotension; Hypovolemia; Lower Body Negative Pressure; Male; Middle Aged; Myocardial Contraction; Renal Dialysis; Stroke Volume; Sympathetic Nervous System

Acute hypotension, transient hypoxaemia and elevation of pulmonary artery pressure are well known to occur during cemented arthroplasty. The aim of this prospective clinical study was to characterize the relationship between plasma concentrations of atrial and brain natriuretic peptides (ANP, BNP), and changes in blood pressure in patients undergoing hip arthroplasty. Elevated ANP and BNP levels may be markers of inadequate myocardial reserve. We measured plasma ANP and BNP levels before the operation and 20 minutes after the cementing in 18 patients (54-90 yr). We defined a hypotensive response after cementing as a decrease in systolic blood pressure of more than 15 mm Hg below the pre-cementing value. In the hypotensive group, preoperative values of ANP were 123 +/- 48.5 pg/ml and BNP, 138 +/- 71.7 pg/ml. These values are significantly greater than those in the normotensive group (ANP 35.9 +/- 7.7, and BNP 17.2 +/- 3.2 pg/ml). High preoperative values of ANP and BNP are associated with more hypotension during cemented arthroplasty and could provide an indication of which patients are at risk of this complication.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Anesthesia, Intravenous; Anesthetics, Combined; Arthroplasty, Replacement, Hip; Atrial Natriuretic Factor; Biomarkers; Blood Pressure Determination; Bone Cements; Female; Follow-Up Studies; Hemodynamics; Humans; Hypotension; Male; Middle Aged; Natriuretic Peptide, Brain; Perioperative Care; Probability; Propofol; Sensitivity and Specificity

Natrecor (nesiritide) is targeted to acute decompensating CHF patients.

Topics: Atrial Natriuretic Factor; Cardiotonic Agents; Drug Costs; Dyspnea; Heart Failure; Hospitalization; Humans; Hypotension; Natriuretic Peptide, Brain; United States

We studied baroreflex gain in inactin-anesthetized mice that had been genetically modified to be depleted of atrial natriuretic peptide (ANP -/-). Wild-type mice (ANP +/+) served as controls. ANP -/- mice had a significantly higher basal arterial blood pressure (ABP) than ANP +/+ mice [112+/-7 vs. 80+/-5 mmHg (mean +/- SEM)]. Their basal heart rates were not different (491+/-13 vs. 446+/-19 bpm). A third group, composed of ANP +/+ mice only, was rendered acutely hypertensive by an intravenous infusion of arginine vasopressin acetate (0.3 pg bolus followed by 0.3 pg/h) so as to serve as a control for the elevated ABP in the ANP -/- mice. Transient changes in ABP were caused by bolus injections of oxymetazoline hydrochloride (1.5-3 ng) or sodium nitroprusside (20-100 ng). Baroreflex gain was calculated as the ratio of the peak heart rate change that followed the peak change in mean ABP resulting from injection of oxymetazoline or nitroprusside. There were no significant differences among the groups in their responses to transient hypertension. On the other hand, the ANP -/- mice showed a significantly depressed tachycardic response to transient hypotension when compared with the other two groups. We conclude that the ANP -/- mice are unable to increase efferent sympathetic nervous activity adequately above the high basal activity that is a feature of this animal model.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Heart Rate; Hypotension; Mice; Mice, Knockout; Pressoreceptors; Tachycardia

Kaliuretic peptide, a 20-amino acid peptide hormone synthesized in the heart, enhances urine flow twofold, whereas atrial natriuretic peptide (ANP) enhances urine flow four- to 11-fold in healthy persons. The present investigation was designed to (1) determine whether kaliuretic peptide may have beneficial diuretic effects in persons with congestive heart failure (CHF), and (2) compare its beneficial effects with ANP in the treatment of CHF. Kaliuretic peptide (100 ng/kg body weight/min) given intravenously for 60 minutes to subjects with New York Heart Association class III CHF increased urine flow fourfold (p <0.001), which was maximal 212 hours after its infusion was stopped. Kaliuretic peptide enhanced sodium excretion threefold in subjects with CHF (p <0.01). Kaliuretic peptide increased the urinary excretion rate of potassium ion and fractional excretion of potassium 3.5- and twofold (p <0.05), respectively. ANP (same concentration) did not significantly enhance urine flow. ANP enhanced sodium excretion two- to sixfold in half of the CHF subjects, whereas it had no effect on sodium excretion in the other half. ANP did not significantly increase fractional excretion of sodium but did increase fractional excretion of potassium (p <0.05) during the first 20 minutes of its infusion. ANP-infused patients with CHF became hypotensive. None became hypotensive secondary to kaliuretic peptide. These data indicate that the diuretic properties of kaliuretic peptide in persons with CHF, as opposed to those of ANP, are not diminished (but rather are increased) compared with their effects in healthy persons. In patients with CHF, kaliuretic peptide causes a natriuresis-a feature not observed in those without sodium retention.

Topics: Adult; Aged; Analysis of Variance; Atrial Natriuretic Factor; Creatinine; Enzyme Inhibitors; Heart Failure; Humans; Hypotension; Infusions, Intravenous; Male; Middle Aged; Potassium; Protein Precursors; Sodium; Treatment Outcome; Urination; Water

Topics: Atrial Natriuretic Factor; Cardiotonic Agents; Half-Life; Heart Failure; Humans; Hypotension; Multicenter Studies as Topic; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic

Hypotension during hemodialysis occurs frequently, but the precise mechanism remains unclear. In this study, the presence of myocardial ischemia and myocardial contractile reserve during infusions of the beta-adrenergic receptor agonist dobutamine was assessed by means of dobutamine-atropine stress echocardiography (DSE) in hypotension-prone (HP) and hypotension-resistant (HR) hemodialysis patients.. Eighteen HP patients (age 53 +/- 6 years) were compared with 18 HR patients (age 53 +/- 3 years), matched with respect to the duration of hemodialysis and cardiovascular history. New wall abnormalities during dobutamine stress reflect the presence of myocardial ischemia, whereas the increase in stroke index and cardiac index reflects myocardial contractile reserve.. Wall motion score at rest (1.42 +/- 0.53 vs. 1.44 +/- 0.57) and dobutamine-induced new wall motion abnormalities (4 vs. 3 patients) between HP and HR patients were similar, but responses of cardiac index, stroke index, and systolic blood pressure to do butamine between the two groups were different. Not withstanding a similar cardiac index at rest (2.4 +/- 1.1 liter/min/m2 in HP and 2.8 +/- 1.2 liter/min/m2 in HR patients), dobutamine-induced increments in the cardiac index were considerably smaller in the former (0.8 +/- 1.3 liter/min/m2) than in the latter patients (2.3 +/- 1.6 liter/min/m2, P = 0.002), predominantly because of a progressive decrease in the stroke index in the HP patients.. Impaired myocardial contractile reserve rather than ischemia is predominant in HP patients. This impaired myocardial contractile reserve may play a role in the development of hemodialysis-induced hypotension.

Topics: Adult; Aged; Atrial Natriuretic Factor; Atropine; Central Venous Pressure; Dobutamine; Echocardiography; Female; Humans; Hypotension; Male; Middle Aged; Myocardial Contraction; Renal Dialysis

The effect of blood volume repletion after frusemide administration on the right atrial and pulmonary artery pressure responses of horses to exercise has not been reported. We examined right atrial and pulmonary artery pressure and plasma atrial natriuretic peptide concentration (ANP) responses to an incremental exercise test in 6 Standardbred mares. Horses were treated, in a 3 way cross over design, with isotonic saline, frusemide (1 mg/kg bwt, i.v.), and frusemide followed 3 h later by lactated Ringer's solution (12 ml/kg bwt, i.v.). Three and a half hours after saline or frusemide administration the horses completed a standard exercise test. Frusemide significantly affected the right atrial and pulmonary artery pressure and ANP responses to exercise. Fluid administration decreased plasma total protein concentrations at rest and during running and abolished the effects of frusemide on the haemodynamic and ANP responses to exercise. These results suggest that the haemodynamic effect of frusemide in running horses is mediated, in large part, by a reduction in plasma and blood volume.

Topics: Animals; Atrial Function, Right; Atrial Natriuretic Factor; Blood Proteins; Blood Volume; Body Weight; Cross-Over Studies; Diuretics; Female; Fluid Therapy; Furosemide; Heart Rate; Hematocrit; Hemodynamics; Horse Diseases; Horses; Hypotension; Isotonic Solutions; Physical Conditioning, Animal; Pulmonary Wedge Pressure; Ringer's Solution; Sodium Chloride

We evaluated the possible role of an imbalance between vasoconstrictor and vasodilator hormones in the pathophysiology of chronic hypotension in uraemia.. Fourteen hypotensive haemodialysed patients, 14 normotensive haemodialysed patients, and 17 control subjects were included in this study. Plasma renin activity (PRA) and plasma levels of catecholamines, angiotensin II (AII), atrial natriuretic peptide (ANP), and arginine vasopressin (AVP) were measured.. The mean time on haemodialysis (HD) was longer in hypotensive patients than in normotensive patients (P < 0.01). Catecholamine levels were higher in the whole group of HD patients than in controls (P < 0.01). Catecholamine levels were higher in hypotensive patients than in normotensive patients, but the differences reached significance only for adrenaline (P < 0.05). PRA and plasma AII levels were higher in hypotensive patients than in the other two groups (P < 0.05), while no differences were observed between normotensive patients and controls. Plasma ANP and AVP levels were higher in HD patients than in controls (P < 0.01), but there were no differences between hypotensive and normotensive patients. In HD patients, mean blood pressure inversely correlated with PRA (r = -0.59, P < 0.01) and plasma AII levels (r = -0.80, P < 0.01).. Our results indicate that in HD patients with chronic hypotension there is an activation of the sympathetic and the renin-angiotensin systems. This activation is probably secondary in an attempt to compensate the vascular resistance to pressor stimuli reported in these patients.

Topics: Adult; Aged; Angiotensin II; Arginine Vasopressin; Atrial Natriuretic Factor; Catecholamines; Chronic Disease; Female; Humans; Hypotension; Male; Middle Aged; Parathyroid Hormone; Renin; Uremia

Topics: Anesthesia, Obstetrical; Anesthesia, Spinal; Atrial Natriuretic Factor; Cesarean Section; Female; Fluid Therapy; Humans; Hypotension; Pregnancy; Research Design

To examine the effect of atrial natriuretic factor (ANF) on renin release induced by renal hypotension, experiments were performed in seven barbiturateanaesthetized dogs with denervated kidneys. Renin release induced by renal arterial constriction to 55 mmHg was measured before and during intrarenal infusion of ANF (200 ng min-1 kg-1 body weight). Before ANF infusion, renal arterial constriction increased renin release from 0.2 +/- 0.1 to 21.8 +/- 3.3 micrograms angiotensin I min-1 (p < 0.05). During ANF infusion renal arterial constriction increased renin release as much as before from 0.8 +/- 0.6 to 23.7 +/- 4.6 micrograms angiotensin I min-1 (p < 0.05). Although ANF increased glomerular filtration rate from 33.9 +/- 4.2 to 43.4 +/- 5.6 ml min-1 (p < 0.05) and sodium excretion from 72 +/- 22 to 567 +/- 112 mumol min-1 (p < 0.05) at normal renal perfusion pressure, ANF was without effect on glomerular filtration rate and sodium excretion during renal arterial constriction. The present study shows that ANF is not an inhibitor of renin release induced by renal arterial constriction in anaesthetized dogs with denervated kidneys. Our findings indicate that ANF does not influence renin release induced by the haemodynamic mechanism.

Topics: Angiotensin I; Animals; Atrial Natriuretic Factor; Constriction; Denervation; Dogs; Female; Glomerular Filtration Rate; Hypotension; Kidney; Male; Natriuresis; Renal Artery; Renin

The effects of a continuous i.v. infusion of urodilatin at a dose of 30 ng kg-1 min-1 were studied in a patient with congestive heart failure. After 30 min, urodilatin had induced a marked stimulation of plasma cyclic GMP concentrations. In parallel haematocrit increased. No significant diuresis and no change of invasive haemodynamics was observed. After 2 h the patient developed a profuse perspiration. Eighty minutes later he suffered from dizziness due to hypotension (blood pressure 80/40 mmHg) and a sudden bradycardia (50 bpm). Urodilatin was discontinued and symptoms were relieved by bed tilt and rapid infusion of isotonic saline solution. Mechanisms contributing to these adverse effects may be fluid extravasation to the third space and sympathoinhibitory effects known to occur with natriuretic peptide infusion.

Topics: Atrial Natriuretic Factor; Blood Pressure; Bradycardia; Cardiac Output; Cyclic GMP; Heart Failure; Heart Rate; Hematocrit; Humans; Hypotension; Infusions, Intravenous; Male; Middle Aged; Peptide Fragments

To study hemodynamic effects on intrarenal oxygenation, O2 microelectrodes were inserted into rat kidneys. In a previous study [M. Brezis, Y. Agmon, and F. H. Epstein. Am. J. Physiol. 267 (Renal Fluid Electrolyte Physiol. 36): F1059-F1062, 1994], we showed that tubular metabolism is a major determinant of intrarenal oxygenation, in part responsible for medullary hypoxia observed under basal conditions. Acute hypotension (by controlled hemorrhage, aortic ligation, or nitroprusside infusion) paradoxically increased medullary PO2 (from 21 +/- 2 to 39 +/- 2 mmHg, P < 0.001) while decreasing cortical PO2 (from 46 +/- 2 to 32 +/- 3 mmHg, P < 0.001), abolishing corticomedullary gradients of oxygen. Laser-Doppler studies indicated that, while cortical blood flow was reduced during hypotension, medullary blood flow was unchanged or increased. The increase in medullary PO2 induced by hypotension was abolished by prior administration of furosemide, suggesting that during hypotension, reduced glomerular filtration rate (GFR), distal delivery, and reabsorption result in decreased oxygen utilization. Acute infusions of atriopeptin III (0.1-1 microgram.kg-1.min-1) decreased both cortical PO2 (from 61 +/- 2 to 55 +/- 2 mmHg, P < 0.001) and medullary PO2 (from 15 +/- 1 to 7 +/- 1 mmHg, P < 0.001), consistent with atriopeptin-induced increases in GFR and tubular reabsorptive work. These data suggest that medullary oxygen availability increases during renal hypoperfusion and may decrease during renal vasodilation.

Topics: Animals; Aorta; Atrial Natriuretic Factor; Blood Flow Velocity; Constriction; Furosemide; Hemodynamics; Hemorrhage; Hypotension; Kidney; Kidney Cortex; Kidney Medulla; Microelectrodes; Nitroprusside; Oxygen Consumption; Rats; Rats, Sprague-Dawley; Vasodilation

Cyclic GMP (cGMP) dependent vasodilating agents (natriuretic peptides, nitric oxide) inhibit secretion of endothelin-1 (ET-1) in cultured endothelial cells. However, in circulatory conditions associated with acute hypotension, a marked increase in plasma ET-1 has repeatedly been observed. Therefore, after administration of cGMP-dependent agents in hypotensive dose, the net effect of these opposing influences on ET-1 release may shed light on the mechanisms determining circulating levels of this peptide. We have studied the effect of a hypotensive dose of atrial natriuretic peptide (n = 16), 8-Br-cGMP (n = 5), and papaverin (n = 7) on plasma ET-1 in anesthetized dogs. All agents produced marked increases in the peptide level at the end of infusion (178, 280, and 240% of the last preinfusion level, respectively) and a mean arterial blood pressure (MAP) decrease of 19, 18, and 42 mmHg (1 mmHg = 133.3 Pa), respectively. In all three protocols, plasma ET-1 continued to rise when the hypotensive agent was discontinued and remained elevated for 2-3 h postinfusion, even though MAP was normalized. There was a close positive correlation between the maximal increment in plasma ET-1 and the maximal decrease in MAP (r = 0.67, p < 0.001). These results show that acute hypotension due to directly acting vasodilators is a potent stimulus for systemic release of ET-1, even when due to agents known to inhibit ET-1 production in cultured endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atrial Natriuretic Factor; Blood Glucose; Blood Pressure; Cyclic GMP; Dogs; Endothelins; Female; Glomerular Filtration Rate; Hypotension; Male; Papaverine

To clarify how plasma atrial natriuretic peptide concentrations vary with the severity of acute lung injury. The influence of coexisting diseases which trigger acute lung injury was also examined.. Prospective study.. Intensive care unit of a university hospital.. Fifty patients who had standard risk factors for acute lung injury including sepsis syndrome, major surgery, prolonged hypotension, aspiration of gastric contents, and burns. Twenty-five of these patients had acute lung injury (group 3) caused by these disorders; the remaining 25 patients had risk factors only (group 2). Ten age-matched normal volunteers were selected as controls (group 1).. None.. Plasma atrial natriuretic peptide concentration was measured in these patients and compared with the severity of acute lung injury. In group 3, a significant increase in the mean plasma atrial natriuretic peptide concentration was observed (188 +/- 78 pg/mL, p < .01) compared with group 2 (54 +/- 28 pg/mL) and the age-matched control group (30 +/- 8 pg/mL). This increase was related to the onset of acute lung injury and returned to control concentrations after recovery. Plasma atrial natriuretic peptide concentrations in group 3 correlated highly with a lung injury score representing the severity of acute lung injury (r2 = .45, p < .01), but did not correlate with other cardiopulmonary variables.. The results suggest that severity of lung injury, but not other predisposing disorders, may be the key factor leading to the increase in plasma atrial natriuretic peptide concentrations observed in these patients.

Topics: Analysis of Variance; Atrial Natriuretic Factor; Burns; Comorbidity; Hemorrhage; Humans; Hypotension; Japan; Linear Models; Pneumonia, Aspiration; Prospective Studies; Respiratory Distress Syndrome; Risk Factors; Systemic Inflammatory Response Syndrome

In urethane-anesthetized rats, sodium L-glutamate (Glu) microinjection into the anteroventral third ventricle region (AV3V) induced a depressor response, but the heart rate remained unchanged, whereas Glu injection into its surrounding areas or normal saline injection into the AV3V had no effect on the arterial pressure and heart rate. Bilateral preinjection of procaine or atriopeptin III antiserum into the nucleus paraventricularis (NPV) and methyl atropine (IV) markedly attenuated the AV3V depressor response, but the hypotensive response was not significantly affected by phentolamine or propranolol (IV), indicating that atriopeptin in the NPV mediates the AV3V depressor response, and excitation of the cardiac vagus is also involved in this response.

Topics: Animals; Atrial Natriuretic Factor; Atropine Derivatives; Blood Pressure; Cerebral Ventricles; Drug Interactions; Hypotension; Hypothalamus; Injections, Intraventricular; Male; Paraventricular Hypothalamic Nucleus; Peptide Fragments; Phentolamine; Procaine; Propranolol; Rats; Rats, Wistar; Sodium Glutamate

We estimated the changes of fluid compartment volumes and concomitant effects on plasma atrial natriuretic peptide (ANP) and plasma renin activity (PRA) for up to 4 hr after intravenous infusion of 57 ml/kg of 1.5% glycine solution over 40 min in six conscious ewes. Infusions of the same volumes of isotonic saline served as controls. Glycine infusions resulted in a four-fold increase and saline in a doubling of the plasma ANP concentration, despite a more pronounced volume expansion from saline. The ANP level remained significantly elevated for 2 hr after glycine infusion. This result suggests that glycine has a specific ANP-stimulating effect which may contribute to the hypovolemia, hypotension, and natriuresis seen in the "transurethral resection (TUR) syndrome." The PRA decreased by about 50% in response to both infusions. However, PRA returned to the baseline level at the end of the glycine infusion, whereas it remained depressed during the entire follow-up period after saline infusion. This is in accordance with a pure volumetric influence on renin release, since calculations of fluid distribution between different compartments suggested that, in contrast to the effect of saline, only a small amount of irrigant water remained in the extracellular fluid after glycine administration. The urea and creatinine clearances increased only in response to isotonic saline. Glycine infusion was even followed by reduction of the creatinine clearance.

Topics: Analysis of Variance; Animals; Atrial Natriuretic Factor; Body Fluid Compartments; Creatinine; Disease Models, Animal; Extracellular Space; Female; Follow-Up Studies; Glycine; Hypotension; Infusions, Intravenous; Kidney; Male; Postoperative Complications; Prostatectomy; Renin; Sheep; Shock; Sodium Chloride; Therapeutic Irrigation; Time Factors; Urea

To determine the role of vasoactive peptides such as endothelin (ET), calcitonin gene-related peptide (CGRP) and human atrial natriuretic peptide (hANP) in the regulation of blood pressure in uremic patients, and to determine the effect of various types of dialyzer membranes on hemodialysis (HD)-induced changes in plasma levels of such peptides, plasma ET, CGRP and hANP were measured in HD patients and patients on continuous ambulatory peritoneal dialysis (CAPD). Plasma levels of ET, CGRP, and hANP were significantly higher in HD and CAPD patients than in healthy subjects. There were no significant differences in plasma levels of ET, CGRP, and hANP between hypertensive and normotensive HD patients, and no significant correlation was observed between HD-induced changes in plasma levels and changes in blood pressure. Plasma levels of ET decreased when HD was performed using high-flux membranes, such as polyacrylonitrile (PAN), polymethyl methacrylate (PMMA) and cellulose triacetate (CTA), but did not decrease using a saponified cellulose (SC) membrane. Plasma levels of CGRP decreased in the case of PAN, but increased significantly with PMMA and showed no change with SC and CTA. Plasma levels of hANP decreased in all types of dialyzer membranes due to decreased secretion. These results indicate that the effect of HD on plasma levels of ET and CGRP, but not hANP, depends on the type of dialyzer membrane used.

Topics: Atrial Natriuretic Factor; Calcitonin Gene-Related Peptide; Endothelins; Female; Humans; Hypotension; Kidneys, Artificial; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis; Uremia

We obstructed renal lymph drainage from a single kidney in diabetic rats who had received 65 mg/kg streptozotocin 6 months prior to the study. Lymphatic obstruction led to a progressive fall in systematic blood pressure from a mean arterial pressure of 101 +/- 5 (SEM) mm Hg (n = 7) to 62 +/- 4 mm Hg (n = 5) (p < .02) after 1.5 h. No change was seen in a sham-operated animal. Despite the decline in systemic blood pressure there was no significant change in the GFR of either kidney. Sodium excretion increased significantly in the experimental kidney. There was no change in the urinary excretion of cyclic GMP from either kidney, and plasma levels of atrial natriuretic peptide (ANP) did not change (55 +/- 21 pg/mL pre- to 64 +/- 18 postobstruction). The results are consistent with a systemic vasodilatation after lymphatic obstruction. The mechanism of this response is still under investigation, but apparently it does not involve ANP.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Diabetes Mellitus, Experimental; Glomerular Filtration Rate; Hypotension; Kidney; Lymphatic System; Male; Natriuresis; Radioimmunoassay; Rats; Rats, Wistar; Vasodilation

It has been postulated that one of the mechanisms of hypotension associated with cirrhosis is an attenuated responsiveness to catecholamines despite the increased activity of the sympathetic nervous system and the elevated plasma concentrations of the sympathetic neurotransmitter, norepinephrine. This abnormality was studied in a dog model of portal hypertension and cirrhosis. Twelve weeks after bile duct ligation (n = 16), intrasplenic pressure rose significantly from 6.3 +/- 0.4 to 14.6 +/- 1.6 mmHg (p < 0.05), mean arterial pressure had fallen from 106 +/- 4 to 83 +/- 8 mmHg (p < 0.01), cardiac output had risen from 3.1 +/- 0.2 to 3.8 +/- 0.8 l/min (p < 0.05) and plasma norepinephrine concentrations rose from 0.22 +/- 0.12 to 1.17 +/- 0.52 nmol/l (p < 0.05). In 7 sham-operated dogs, the changes in these 4 variables over the same period were non-significant. In vivo pressor responsiveness was tested by studying the effects of intravenous and intra-arterial infusions of norepinephrine and the non-selective beta-adrenoceptor agonist, isoproterenol. In vitro responsiveness was tested by measuring the effects of isoproterenol on the isometric twitch of isolated ventricular strips and the effects of norepinephrine on femoral, mesenteric and renal arterial rings. There was no significant change in the in vivo responses of chronic bile-duct-ligated dogs at 12 weeks compared to the preoperative assessment, or to sham-operated dogs at 12 weeks. Furthermore, there was no significant difference between the in vitro responses of ventricular strips to isoproterenol or arterial rings to norepinephrine prepared from chronic bile-duct-ligated and sham-operated dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aldosterone; Animals; Arteries; Atrial Natriuretic Factor; Bile Ducts; Bilirubin; Blood Pressure; Dogs; Dose-Response Relationship, Drug; Hypertension, Portal; Hypotension; In Vitro Techniques; Isoproterenol; Liver Cirrhosis, Experimental; Liver Function Tests; Muscle Contraction; Muscle, Smooth, Vascular; Norepinephrine; Plasma Volume; Reference Values; Renin; Serum Albumin; Sodium; Sodium, Dietary; Time Factors

Hypotension is a frequent complication in patients subjected to regular hemodialysis. Insufficient regulation of blood pressure following dialysis with ultrafiltration has been attributed to a lack in hormone activation. To determine whether altered production of vasoactive hormones is involved in the breakdown of blood pressure regulation during hemodialysis (HD), blood volume (BV), atrial natriuretic peptide (ANP), plasma renin activity (PRA), aldosterone (Aldo), norepinephrine (NE), epinephrine (Epi), intact immunoreactive parathyroid hormone (iPTH) and arginine vasopressin (AVP) were examined. The relative BV was measured by continuous hemoglobinometry during the HD period of about 240 min. The total decrease in BV at the end of treatment was 23.5 +/- 4.8% of the pretreatment value. Systolic blood pressure (SBP) was 99.6 +/- 23.0 mmHg before dialysis compared with 74.6 +/- 18.8 mmHg at the end of dialysis and heart rate (HR) increased from 76.3 +/- 5.5/min before to 92.0 +/- 10.0/min at the end of dialysis. Despite the wide range of interindividual variance, the hormonal changes indicate that hypotensive patients under HD develop reduced sensitivity of the angiotensin-renin, adrenergic and AVP systems to volumetric stimuli. A paradoxical activation in iPTH and PRA independent Aldo secretions is apparent.

Topics: Aldosterone; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Blood Volume; Epinephrine; Female; Heart Rate; Hormones; Humans; Hypotension; Kidney Failure, Chronic; Male; Middle Aged; Norepinephrine; Parathyroid Hormone; Renal Dialysis; Renin

In order to clarify the pathogenesis of hypotension seen in the patients on chronic hemodialysis, we studied the vascular reactivity to exogenous vasoactive substances and the change of plasma ANP level during hemodialysis treatment. The vascular responsiveness to intravenously infused norepinephrine was decreased in hemodialysis patients, particularly in hypotensive group, compared with healthy controls (< 0.05). The blood pressure response to angiotensin II was also diminished significantly in hypotensive patients, compared with normotensive patients (p < 0.05). The plasma ANP concentration before and after each hemodialysis treatment was not different statistically between hypotensive and normotensive patients. Furthermore, the change of plasma ANP concentration was not correlated with the blood pressure change during each hemodialysis procedure. These findings suggest that the decrease of vascular responsiveness may be a factor for causing persistent hypotension in patients on chronic hemodialysis, and that the plasma ANP level is not responsible for the pathogenesis of hypotension.

Topics: Adult; Aged; Angiotensin II; Atrial Natriuretic Factor; Female; Humans; Hypotension; Male; Middle Aged; Norepinephrine; Renal Dialysis; Vascular Resistance; Vasomotor System

We have reported that increased left heart pressure inhibits increases in plasma renin activity (PRA), arginine vasopressin (AVP), and cortisol during arterial hypotension. The goal of this study was to determine whether increases in right heart pressure also inhibited hormonal responses to hypotension. Seven dogs were chronically instrumented with inflatable cuffs around the ascending aorta (AA), the pulmonary artery (PA), and the thoracic inferior vena cava (IVC), as well as with catheters in both atria, the abdominal aorta, and vena cava. The IVC, the PA, and the AA cuffs were inflated on different days to cause step reductions in mean arterial pressure (MAP) of 5, 10, 20, and 30% below control MAP. Graded constriction of the AA caused large increases in left atrial pressure and plasma atrial natriuretic peptide (ANP), but had no effect on plasma AVP or cortisol and caused only a small increase in PRA at the maximal reduction of MAP. Constriction of the IVC reduced both atrial pressures and plasma ANP, but stimulated increases in PRA, AVP, and cortisol. Constriction of the PA increased right atrial pressure and plasma ANP and caused increases in plasma AVP and cortisol that were similar to responses during IVC constriction, but the PRA response was only half (P < 0.05). These results indicate that increasing pressure on the right side of the heart can attenuate the PRA response to hypotension, and suggest that the inhibition is mediated by the rise in plasma ANP.

Topics: Animals; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Constriction, Pathologic; Dogs; Female; Heart Conduction System; Hydrocortisone; Hypotension; Male; Pressoreceptors; Pulmonary Artery; Renin; Vena Cava, Inferior

The aim of the study was to find out whether vasopressin (AVP) modifies hypotensive and heart rate accelerating effects of atrial natriuretic peptide (ANP) in normotensive (WKY) and spontaneously hypertensive (SHR) conscious rats. The effect of i.v. administration of 1; 2 and 4 micrograms of ANP on blood pressure (MP) and heart rate (HR) was compared during i.v. infusion of 0.9% NaCl (NaCl), NaCl+AVP (1.2 ng kg-1 min-1) and NaCl+dEt2AVP (V1 receptors antagonist, 0.5 microgram kg-1 min-1). AVP increased MP in SHR and WKY and decreased HR in SHR. V1 antagonist decreased MP and increased HR only in SHR. In SHR ANP decreased MP and increased HR during NaCl, AVP and V1 antagonist infusion. In WKY these effects were observed only during AVP administration. In each experimental situation hypotension and tachycardia induced by ANP were greater in SHR than in WKY. In both strains ANP induced changes in MP and HR were enhanced during AVP in comparison to NaCl infusion. V1 antagonist did not modify effects of ANP in WKY and SHR. The results indicate that ANP abolishes hypertensive response induced by blood AVP elevation and that the basal levels of endogenous vasopressin acting through V1 receptors does not interfere with hypotensive action of ANP neither in WKY nor in SHR.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Drug Interactions; Heart Rate; Hypotension; Male; Peptide Fragments; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Sodium Chloride

The pharmacological activities of synthetic mammalian brain natriuretic peptides (BNP) from the human, pig and rat were examined in rats. These peptides all elicited diuresis and hypotension, relaxed isolated rat aorta, augmented cyclic GMP concentration in cultured rat vascular smooth muscle cells, and bound to the cells with a high affinity. Pig and rat BNPs were as active as atrial natriuretic peptides from the human and the rat (alpha-hANP and alpha-rANP) for the diuretic and hypotensive effects as well as for cyclic GMP augmentation, while human BNP was about 10 times less potent. Rat BNP was not as active as the other peptides in competing with the binding of [125I]alpha-hANP to rat vascular smooth muscle cells. Thus, the BNPs did not have identical pharmacological profiles although the potencies of the peptides for cyclic GMP augmentation correlated well to those for vasorelaxation.

Topics: Amino Acid Sequence; Animals; Atrial Natriuretic Factor; Binding, Competitive; Brain; Cells, Cultured; Cyclic GMP; Diuretics; Humans; Hypotension; Male; Molecular Sequence Data; Muscle Relaxation; Muscle, Smooth, Vascular; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Rats; Rats, Inbred Strains; Recombinant Proteins; Swine

Acute hypoxia elicits diuresis, natriuresis, and hypotension in many mammalian species, but the cause of this effect remains unclear. The present study, using chronically instrumented rats, was undertaken to assess a possible role of atrial natriuretic factor (ANF) in these hypoxic responses. Acute hypoxia (10.5% O2) increased urine output and sodium and potassium excretion. Systemic arterial blood pressure fell during acute hypoxia. Levels of ANF significantly increased with acute hypoxia. The plasma levels of ANF during acute hypoxia were similar to those found following bolus doses of exogenous ANF which are known to cause diuresis, natriuresis and a fall in blood pressure. Increased ANF levels may play a role in mediating physiologic responses to hypoxia in the rat.

Topics: Animals; Atrial Natriuretic Factor; Diuresis; Hypotension; Hypoxia; Male; Natriuresis; Potassium; Rats; Rats, Inbred Strains

Synthetic alpha-human atrial natriuretic peptide (alpha-hANP), 1 micrograms/kg, was intravenously given to 16 cirrhotic patients with ascites and 9 control subjects (CS) to investigate major factors responsible for sodium retention and refractory ascites. The following parameters were measured before and after alpha-hANP administration; such as lithium clearance (CLi) as an index of fluid delivery to the distal tuble, mean arterial pressure (MAP), urinary sodium excretion rate (UNaV), urine volume (V), glomerular filtration rate (GFR), effective renal plasma flow (ERPF), plasma renin activity (PRA), plasma aldosterone concentration (PAC), urinary excretion of prostaglandin (PG)E2, 6-keto-PGF1 alpha (6-k-PGF1 alpha), and thromboxane B2 (TxB2). Patients were divided following alpha-hANP administration into 2 groups as "good responders (GR)" and "poor responders (PR)", in which GR was defined as the group showing 2-fold-increase in UNaV. In contrast, PR had significant lower MAP (71.8 +/- 5.04 mmHg), GFR (21.3 +/- 3.90 ml/min), ERPF (158.0 +/- 43.8 ml/min), FELi (CLi/GFR; 12.6 +/- 1.26%), and higher PRA (8.72 +/- 0.99 ng/ml/h) and PAC (12.2 +/- 3.13 ng/dl) than GR. GR demonstrated almost same natriuretic response as CS with an increase of GFR and renal PGs synthesis, and a decrease of FELi despite reduction in blood pressure. However, alpha-hANP did not suppress PRA, PAC, and distal tubular reabsorption of sodium (FDRNa = 1-FENa/FELi) in cirrhotic patients, whereas suppressed in CS. UNaV correlated with FELi (r = 0.687, p = 0.01) and GFR (r = 0.777, p = 0.01). PRA correlated with FELi r = 0.669, p = 0.015), GFR (r = -0.634, p = 0.018), and MAP (r = 0.858, p = 0.001) only in cirrhosis. These results therefore indicated that hypotension caused by hemodynamic alteration and extremely stimulated renin release might effect on proximal tubular sodium reabsorption and GFR, leading to sodium retention and diuretic resistance in cirrhosis.

Topics: Angiotensin II; Ascites; Atrial Natriuretic Factor; Female; Glomerular Filtration Rate; Humans; Hypotension; Kidney Function Tests; Kidney Tubules; Lithium; Liver Cirrhosis; Male; Middle Aged; Renin; Sodium

To determine if circulating levels of atrial natriuretic factor comparable with those seen in pathophysiologic states alter autonomic control of the circulation, direct recordings of hemodynamic variables and efferent sympathetic nerve activity to muscle (microneurography) were obtained during two separate protocols in a total of 21 normal men (age 25 +/- 1 years). In protocol 1, the responses of 10 men were compared during incremental mechanical unloading of cardiopulmonary baroreceptors with lower body negative pressure versus responses to comparable unloading during infusion of alpha-human atrial natriuretic factor. Lower body negative pressure decreased pulmonary artery diastolic and right atrial pressures, did not alter arterial pressure or heart rate and increased muscle sympathetic nerve activity from 205.2 +/- 36.3 to 438.7 +/- 100.2 units/min (p less than 0.01). Intravenous infusion of atrial natriuretic factor (25 ng/kg per min) increased plasma levels of the hormone from 24 +/- 4 to 322 +/- 34 pg/ml (p less than 0.01, n = 6), produced similar decreases in pulmonary artery diastolic and right atrial pressures, did not alter arterial pressure, increased heart rate and increased sympathetic nerve activity from 233.1 +/- 35.6 to 387.2 +/- 64.9 units/min (p less than 0.05). Thus, during similar hemodynamic perturbations produced by lower body negative pressure or infusion of atrial natriuretic factor at the dose used in this study, these subjects exhibited comparable sympathoexcitatory responses, with a 109 +/- 23% increase in sympathetic activity during lower body negative pressure and a 76 +/- 19% increase during atrial natriuretic factor infusion (p = NS). In protocol 2, the responses of 11 additional men were examined during lower body negative pressure performed before and again during infusion of atrial natriuretic factor (12.5 ng/kg per min). During baseline (prehormone) trials, lower body negative pressure (-14.5 +/- 1.6 mm Hg) decreased central venous pressure, did not change arterial pressure or heart rate and increased sympathetic nerve activity from 215 +/- 47.7 to 372.3 +/- 64.3 units/min (p less than 0.001). Infusion of atrial natriuretic factor increased plasma levels of the hormone from 39 +/- 8 to 313 +/- 18 pg/ml (p less than 0.01, n = 7); central venous pressure was held constant during hormone infusion by intravenous infusion of saline solution.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adult; Atrial Natriuretic Factor; Cold Temperature; Forearm; Hemodynamics; Humans; Hypotension; Lower Body Negative Pressure; Male; Reflex; Sympathetic Nervous System; Vascular Resistance

Experiments were conducted to determine if hypotensive responses to chicken cardiac hypotensive extract (CHE) or synthetic rat atrial natriuretic peptide (ANP) are affected by dietary sodium. The CHE was significantly more hypotensive in chickens fed high-sodium diets than in chickens fed low-sodium diets. Atrial natriuretic peptide was equally hypotensive in both groups. Experiments were also conducted to determine whether CHE inhibits the hypertensive response to arginine vasotocin (AVT), the avian antidiuretic hormone. The acute hypertensive response to AVT was inhibited by CHE; and CHE reversed the AVT-induced increase in the baseline mean arterial blood pressure.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Chickens; Female; Hypotension; Kidney; Myocardium; Poultry Diseases; Random Allocation; Sodium; Sodium, Dietary; Tissue Extracts; Vasotocin

We have purified and isolated a novel, hypotensive peptide from avian ventricular tissue. Ventricular homogenates have been shown to exhibit potent hypotensive activity in the avian and mammalian species, with little natriuresis or diuresis. Using avian mean arterial pressure (MAP) as a bioassay, we were able to purify a peptide which decreased MAP 30% in adult, female chickens. Amino acid analysis indicated that it contained 20 amino acids (including two cysteine residues), and was not similar to the amino acid composition of mammalian atrial natriuretic factors, or other known hypotensive peptides.

Topics: Amino Acids; Animals; Atrial Natriuretic Factor; Chickens; Chromatography, High Pressure Liquid; Heart Ventricles; Hypotension

Our earlier studies have demonstrated that atrial natriuretic factor (ANF) can produce hypotensive, natriuretic and diuretic effects and that changes in the renal nerve activity can alter the renal excretory function. A few previous studies suggested that ANF could change the renal nerve activity. Thus, the present study was designed to assess the role of the renal nerve in the natriuretic and diuretic effect of ANF. Experiments were conducted on four groups of anesthetized Sprague-Dawley rats: normal control rats, unilateral acute renal denervated rats with and without ANF administration and chronic renal denervated rats. The arterial blood pressure and the renal function responses to intravenous infusion of graded doses of ANF (atriopeptin III. 0.15, 0.30 and 0.45 microgram/kg.min) were studied. In normal rats, infusion of ANF significantly decreased the mean arterial blood pressure in a dose-related pattern (from 109 +/- 2 to 107 +/- 3, 102 +/- 4 and 89 +/- 5 mmHg, respectively). The glomerular filtration rate (GFR) did not change significantly whereas the urine flow and the absolute and the fractional excretion rates of sodium and potassium were significantly increased. Renal denervation alone did not change the blood pressure and GFR, but produced ipsilateral diuresis and saluresis without changing the function of the contralateral kidney. Subsequent administration of ANF decreased the blood pressure but did not affect bilateral GFR. There were significant increments in the urine flow and the excretions of sodium and potassium in both the denervated and the contralateral kidneys. Infusion of ANF into chronic renal denervated rats also reduced the blood pressure and increased the renal excretion of water and sodium. These results indicate that the diuretic and the natriuretic effects of ANF is not resulted from a decreased activity of the renal efferent nerve and that the hypotensive and the renal effects of ANF are independent of renal innervation.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Denervation; Diuresis; Glomerular Filtration Rate; Hypotension; Kidney; Male; Natriuresis; Rats; Rats, Inbred Strains

Chronic regulation of the cardiovascular system by atrial natriuretic factor was investigated by generating transgenic mice with elevated hormone levels in the systemic circulation. A fusion gene comprising the mouse transthyretin promoter and mouse atrial natriuretic factor structural sequences was designed so as to target hormone expression to the liver. Hepatic expression of atrial natriuretic factor was detectable as early as embryonic day 15 in transgenic animals. In adult transgenic mice, plasma immunoreactive atrial natriuretic factor concentration was elevated at least eightfold as compared with nontransgenic littermates. The mean arterial pressure of conscious transgenic mice was 75.5 +/- 0.9 mm Hg, significantly less than that of nontransgenic siblings (103.9 +/- 2.0 mm Hg). This difference in mean arterial pressure was not accompanied by significant changes in several other physiological parameters, including heart rate, plasma and urinary electrolytes, water intake, and urine volume. This study demonstrates that a chronic elevation of plasma atrial natriuretic factor decreases arterial blood pressure without inducing diuresis and natriuresis in transgenic mice and also illustrates the value of the transgenic approach for the study of the cardiovascular system.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Cloning, Molecular; Gene Expression; Hypotension; Mice; Mice, Inbred C3H; Mice, Transgenic; Prealbumin

Increased capillary permeability and severe hypotension represent the two major cardiovascular complications of IL-2 immunotherapy. The mechanisms responsible for IL-2 cardiovascular toxicity are still obscure. Since increased vascular permeability and vasodilatation may be also induced by the cardiac hormone atrial natriuretic peptide (ANP), we have evaluated ANP concentrations in relation to mean arterial pressure in one patient with metastatic renal carcinoma, treated with a 24-h intravenous infusion of IL-2 at a dose of 3 x 10(6) Cetus U/m2/day for 5 days. The results showed that episodes of important hypotension were associated with abnormally high plasma levels of ANP. Owing to its vasodilator activity, exaggerated ANP secretion, perhaps due to an inappropriate cardiac endocrine function in response to hemodynamic changes induced by IL-2, may play a role in hypotension, which occurs during IL-2 immunotherapy for cancer.

Topics: Atrial Natriuretic Factor; Capillary Permeability; Drug Administration Schedule; Female; Humans; Hypotension; Interleukin-2; Kidney Neoplasms; Lung Neoplasms; Middle Aged; Vaginal Neoplasms

Changes in the arterial pressure (AP), heart rate (HR) and sensitivity of chronotropic baroreceptor reflex (SBR) evoked by i. v. infusion of alpha-ANP, AP-III, AP-II, and AP-I (1 mg/kg/min) were studied in alert Wistar rats. The SBR was tested by infusion of phenylephrine or sodium nitroprusside. All the ANP analogues, except AP-1, were shown to decrease the AP and evoke differential changes in the SBR. The SBR evoked by phenylephrine was increased by 60-80%, whereas SBR evoked by sodium nitroprusside was decreased by 30-60%. The specific changes in tachycardic and bradycardic components of the baroreceptor reflex after ANP analogues infusions seem to reflect participation of the baroreceptor reflex in the mechanism of ANP-induced hypotension.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Heart Rate; Hypotension; Male; Pressoreceptors; Rats; Reflex

The adrenergic response to an episode of bradycardia and hypotension associated with atrial natriuretic factor and prostaglandin infusion in a healthy male subject is described. Noradrenaline levels did not change despite a profound fall in blood pressure. In contrast, there was an almost thirty-fold increase in adrenaline levels. This dissociated sympathoadrenal response suggests activation of the Bezold-Jarisch reflex.

Topics: Adrenal Glands; Adult; Atrial Natriuretic Factor; Bradycardia; Dinoprostone; Epinephrine; Humans; Hypotension; Infusions, Intravenous; Male; Norepinephrine; Renin; Sympathetic Nervous System

Atrial natriuretic factor was infused in a low dose (0.2 microgram/min) during 5 days in six patients with essential hypertension. Atrial natriuretic factor infusion caused plasma levels of atrial natriuretic factor to increase from 49 +/- 10 to 106 +/- 19 pg/ml. Within 4 hours after the start of the atrial natriuretic factor infusion, urinary sodium excretion increased in all subjects. Sodium balance was regained after 24 hours with a net loss of 72.3 +/- 14.6 mmol. However, systolic as well as diastolic blood pressure started to decrease gradually in all subjects only after 12 hours of atrial natriuretic factor infusion, reaching a stable level after 36 hours with a decrease of 11.5 +/- 1.5% and 10.3 +/- 0.8%, respectively. Heart rate increased in parallel by 12.6 +/- 3.1%. Hematocrit rose 7.1 +/- 2.3%. After cessation of atrial natriuretic factor infusion, plasma atrial natriuretic factor levels, sodium balance, and hematocrit returned to baseline within 24 hours, whereas blood pressure slowly returned toward baseline values over 3 days. These data show that chronic atrial natriuretic factor infusion in patients with essential hypertension causes a negative sodium balance and a rise in hematocrit, followed by a smooth decrease in blood pressure with a rise in heart rate until a new equilibrium is reached after approximately 2 days. Thus, atrial natriuretic factor in low doses appears intimately involved in the regulation of sodium balance and blood pressure in humans. Moreover, these data suggest that atrial natriuretic factor-like substances will eventually become useful antihypertensive drugs.

Topics: Antihypertensive Agents; Atrial Natriuretic Factor; Blood Pressure; Humans; Hypotension; Infusions, Intravenous; Male; Middle Aged; Natriuresis; Time Factors

The aim of this paper was to study plasma atrial natriuretic factor, renin activity, aldosterone and antidiuretic hormone in low-output heart failure syndromes such as cardiogenic shock, hypovolemic shock and hypotension with bradycardia syndrome. A total of 30 patients were investigated: 10 with cardiogenic shock due to acute myocardial infarction of the anterior wall (systolic and diastolic blood pressure 56.0 +/- 3.7/40.5 +/- 2.0 mmHg; heart rate 119.7 +/- 1.2 beats/min; central venous pressure 16.2 +/- 0.6 cmH2O) (I group), 10 with hypovolemic shock induced by melena in peptic ulcer (systolic and diastolic blood pressure 74.5 +/- 1.5/57.5 +/- 1.7 mmHg; heart rate 111.0 +/- 1.4; central venous pressure 6.3 +/- 0.5 cmH2O) (II group), 10 with hypotension with bradycardia syndrome which occurred in patients during acute myocardial infarction of the inferior wall (systolic and diastolic blood pressure 71.9 +/- 2.0/58.0 +/- 2.6 mmHg; heart rate 52.0 +/- 2.2 beats/min; central venous pressure 4.6 +/- 0.4 cmH2O) (III group). Plasma atrial natriuretic factor values were measured using radioimmunoassay after chromatographic pre-extraction; plasma renin activity, aldosterone and antidiuretic hormone values were calculated using radioimmunoassay. Circulating atrial natriuretic factor was significantly (p less than 0.01) higher in patients with cardiogenic shock (102.4 +/- 7.4 pg/ml) than in healthy volunteers (8.4 +/- 0.3 pg/ml). In the former there was a positive correlation between atrial natriuretic factor and central venous pressure values. Atrial natriuretic factor and central venous pressure values in the IInd and IIIrd groups of patients were in the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aldosterone; Atrial Natriuretic Factor; Bradycardia; Cardiac Output, Low; Female; Hemodynamics; Humans; Hypotension; Male; Middle Aged; Myocardial Infarction; Renin; Shock; Shock, Cardiogenic; Vasopressins

The natriuretic effect of pharmacological doses of atrial natriuretic peptide (ANP) is markedly reduced in cirrhosis with ascites. The current study, which includes two protocols, was carried out to investigate whether this phenomenon is related to the altered systemic hemodynamics present in cirrhosis. In protocol A, the administration of ANP (2.5 micrograms.kg-1 as a bolus followed by a constant infusion of 0.1 microgram.kg-1.min-1) to 10 rats with carbon tetrachloride-induced cirrhosis and ascites produced a significantly lower increase in diuresis (13.4 +/- 1.3 microliters/min) and natriuresis (2.3 +/- 0.3 mu Equiv/min) than in 10 control rats (56.3 +/- 1.4 microliters/min and 8.7 +/- 0.5 mu Equiv/min, respectively), indicating a renal resistance to the effect of ANP in this experimental model of cirrhosis. The reduction of arterial pressure induced by ANP was similar in both groups. However, since baseline mean arterial pressure was significantly lower in cirrhotic rats, the degree of hypotension during ANP infusion was also greater in this group of animals (82 +/- 3 vs. 109 +/- 2 mmHg). The aim of protocol B was to assess whether normalization of arterial pressure in cirrhotic rats increases the renal response to ANP. This protocol includes two groups of 10 rats with cirrhosis and ascites infused with a glucose solution containing norepinephrine (CT-NE rats) or angiotensin II (CT-AII rats) at doses to normalize arterial pressure and an additional control group of 10 cirrhotic rats with ascites receiving only glucose solution (CT rats). Angiotensin II, but not norepinephrine or glucose solution administration, was associated with a significant increase in urine volume and sodium excretion. During ANP infusion, CT rats showed a blunted diuretic and natriuretic response. In contrast, the ANP-induced increase in urine volume and sodium excretion observed in CT-NE (53.6 +/- 10.4 microliters/min and 9.3 +/- 2.2 mu Equiv/min) and CT-AII rats (98.3 +/- 11.6 microliters/min and 15.5 +/- 2.9 mu Equiv/m), was similar or even greater than that showed by the healthy rats of protocol A. The degree of hypotension during ANP administration was also similar (CT-NE, 104 +/- 2; CT-AII, 108 +/- 5 mmHg). These results suggest that the blunted response to pharmacological doses of ANP in cirrhosis with ascites is related to altered systemic hemodynamics of cirrhosis, which further deteriorates during the infusion of the peptide.

Topics: Angiotensin II; Animals; Atrial Natriuretic Factor; Blood Pressure; Hemodynamics; Hypotension; Infusions, Intra-Arterial; Kidney; Liver Cirrhosis, Experimental; Male; Norepinephrine; Phenobarbital; Rats; Rats, Inbred Strains

Plasma immunoreactive atrial natriuretic factor (irANF) levels and the effects of alpha-human ANF (alpha-hANF) infusion were investigated in 7 patients with liver cirrhosis and ascites. Under basal conditions, supine blood pressure (BP) averaged 136/76 +/- 9/4 mm Hg (mean +/- SEM). Plasma irANF concentrations (124 +/- 33 pg/ml) were higher (p less than 0.01) than those in age-matched normal subjects (47 +/- 5 pg/ml). Plasma renin activity (PRA 5.9 +/- 2.2 ng/ml/h), aldosterone (18 +/- 7 ng/dl) and norepinephrine (NE, 66 +/- 5 ng/dl) levels were also elevated compared to the age-related normal range. Alpha-hANF infusion for 60 min at 0.036 micrograms/kg/min decreased the mean BP (-14%; p less than 0.05), increased PRA (+179%; p less than 0.05) and plasma NE (+24%; p less than 0.05). Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), diuresis and natriuresis were not modified. A subsequent 60-min infusion of alpha-hANF at 0.067 micrograms/kg/min produced a marked fall in mean BP (-26%; p less than 0.001), hemoconcentration (hematocrit +6%; p less than 0.001) despite stable body fluid balance and a further increase in PRA (+350%, p less than 0.005). GFR and ERPF were severely reduced (-55 and -56%, respectively; p less than 0.001), while diuresis and natriuresis were not modified. Plasma aldosterone was unaltered during, but rose (+72%; p less than 0.01) after the cessation of alpha-hANF infusion. Variations in natriuresis during alpha-hANF infusion correlated positively with BP (r = 0.47; p less than 0.01), ERPF (r = 0.53; p less than 0.01) or GFR (r = 0.51; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aldosterone; Ascites; Atrial Natriuretic Factor; Blood Pressure; Catecholamines; Female; Heart Rate; Humans; Hypotension; Kidney; Kidney Function Tests; Liver Cirrhosis; Male; Middle Aged; Norepinephrine; Posture; Radioimmunoassay; Renin; Time Factors

Intravenous injection of dynorphin A-(1-10) amide (Dyn, 81-324 nmol/kg) induced a dose-dependent hypotensive effect in the rat. This effect was antagonized by pretreatment with immunoglobulin G, purified from a specific antiserum raised against alpha-human atrial natriuretic peptide (anti-hANP-IgG), as well as by high doses of naloxone (2 or 10 mg/kg). In addition, a 12-fold increase in plasma level of atrial natriuretic peptide-like immunoreactivity (ANP-IR) was found following Dyn administration, which was accompanied by a significant decrease of atrial ANP-IR. These results suggest that the stimulated release of ANP-IR from the atrium may constitute one of the mechanisms for the depressor effect of dynorphin peptides.

Topics: Animals; Atrial Natriuretic Factor; Dose-Response Relationship, Drug; Dynorphins; Heart Atria; Hypotension; Immunoglobulin G; Male; Myocardium; Peptide Fragments; Rats; Rats, Inbred Strains; Time Factors

Hypotensive hemorrhage (HH) is characterized by intravascular volume depletion, avid renal sodium retention, and activation of the renin-angiotensin-aldosterone system (RAAS). The current studies were designed to investigate whether intravascular volume depletion would modulate circulating atrial natriuretic factor (ANF) and, further, to examine what contribution, if any, a decrease in ANF would have in mediating the antinatriuresis and RAAS stimulation associated with HH. Two groups of anesthetized dogs underwent controlled arterial hemorrhage to reduce mean arterial pressure by 15-20 mmHg. Data were collected before and immediately after HH. One group (n = 6) underwent hemorrhage alone, whereas a second group (n = 5) underwent HH with simultaneous administration of alpha-human ANF (2.5 ng.kg-1.min-1), a dose calculated to prevent a reduction in ANF. In the untreated group, circulating ANF was significantly reduced after hemorrhage (79.4 +/- 7.4 to 57.2 +/- 3.4 pg/ml, P less than 0.05), whereas in the treated group ANF increased significantly (73.5 +/- 12.2 to 147.4 +/- 17.2 pg/ml, P less than 0.05). Despite differences in circulating ANF, both groups had similar reductions in urinary sodium excretion and renal blood flow, and similar increases in plasma renin activity. These studies demonstrate that circulating ANF is significantly reduced in HH; however, the mechanism of antinatriuresis and activation of the RAAS is independent of the reduction in circulating ANF.

Topics: Aldosterone; Animals; Atrial Natriuretic Factor; Dogs; Female; Hemorrhage; Hypotension; Kidney; Male; Natriuresis; Renin; Renin-Angiotensin System

We examined a possible interaction between the calcium entry blocker nifedipine and atrial natriuretic peptide on blood pressure and natriuresis in anesthetized rabbits. The administration of atrial natriuretic peptide (0.05 micrograms/kg/min) produced a significant decrease in mean arterial pressure. Similar reductions in blood pressure were obtained during the administration of nifedipine (1.0 micrograms/kg/min). Atrial natriuretic peptide produced a consistent increase in glomerular filtration rate that was higher than the increase in renal blood flow; hence, the filtration fraction was significantly elevated. Atrial natriuretic peptide also elicited a significant increment in urine volume and urinary sodium excretion, while nifedipine was devoid of any significant effects on renal hemodynamics and renal excretory function during the experimental period. The administration of atrial natriuretic peptide superimposed on an ongoing infusion of nifedipine resulted in a greater fall of blood pressure than that seen during the administration of atrial natriuretic peptide or nifedipine alone. Sodium excretion was also potentiated, but there were no changes in renal hemodynamics or in the filtration fraction. These results suggest that calcium entry blockers potentiate the vasodepressor and the natriuretic effects of atrial natriuretic peptide but prevent its renal hemodynamic effects.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Creatinine; Drug Synergism; Female; Hypotension; Natriuresis; Nifedipine; Rabbits; Renal Circulation; Vascular Resistance

The effects of synthetic Atrial Natriuretic Factor (ANF) on urine flow rate, sodium excretion, potassium excretion and arterial blood pressure were studied in 10-12 days-old female calves. In four female calves fitted with a Foley catheter, an intravenous administration of ANF (Ile-ANF 26; 1.6 micrograms/kg body wt during 30 min) induced an increase (P less than 0.01) in urine flow rate (from 1.8 +/- 0.2 to 12.8 +/- 1.1 ml/min), sodium excretion (from 0.15 +/- 0.02 to 0.81 +/- 0.06 mmol/min) and free water clearance (from 0.13 +/- 0.9 to 5.16 +/- 0.5 ml/min). It had no significant effect on potassium excretion. In four calves chronically-instrumented with a carotid catheter, an intravenous administration of synthetic ANF alone (1.6 micrograms/kg body wt during 30 min) induced a gradual decrease (P less than 0.01) in systolic, diastolic and mean arterial blood pressure (from 112 +/- 4 to 72, from 72 +/- 2 to 61 +/- 1 and from 90 +/- 2 to 65 +/- 2 mmHg respectively, at the end of ANF infusion). An intravenous administration of angiotensin II (AII) (0.5 micrograms/kg body wt during 45 min) induced a significant increase in systolic, diastolic and mean arterial blood pressure which was antagonized by an i.v. bolus injection of ANF (0.125 micrograms/kg body wt). However, during a simultaneous administration of AII (0.3 micrograms/kg body wt during 30 min) and ANF (1.6 micrograms/kg body wt. during 30 min), the atrial peptide did not influence the pressure action of AII. These findings indicate that the conscious newborn calf is sensitive to diuretic, natriuretic and hypotensive effects of synthetic ANF.

Topics: Angiotensin II; Animals; Animals, Newborn; Atrial Natriuretic Factor; Blood Pressure; Cattle; Diuresis; Female; Hypotension; Osmolar Concentration; Potassium; Sodium

In patients with congestive heart failure, atrial natriuretic factor may serve as a counter-regulatory hormone, offsetting the vasoconstrictive and volume-retentive effects of the sympathetic nervous system, the renin-angiotensin-aldosterone system and vasopressin. Indeed, the plasma levels of atrial natriuretic factor and the vasoconstrictor hormones are often simultaneously elevated in these patients. It is not known, however, whether atrial natriuretic factor remains responsive to sudden reductions in atrial pressure in patients with chronic heart failure, or is unresponsive like the vasoconstrictor systems. To examine this issue, the plasma concentrations of atrial natriuretic factor and the vasoconstrictor hormones were measured in 20 normal subjects and 12 patients with chronic congestive heart failure during incremental lower body negative pressure, an intervention that lowers atrial pressure. In the normal subjects, incremental lower body negative pressure at -10, -20 and -40 mm Hg decreased central venous pressure and pulse pressure. At maximal lower body negative pressure, plasma atrial natriuretic factor levels decreased from 51 +/- 5 to 27 +/- 3 pg/ml (p less than 0.01), whereas increases occurred in plasma levels of norepinephrine (194 +/- 11 to 385 +/- 70 pg/ml, p less than 0.01), renin activity (1.4 +/- 0.2 to 3.9 +/- 0.1 ng/ml per h, p less than 0.01) and vasopressin (1.3 +/- 0.1 to 6.4 +/- 2.4 pg/ml, p less than 0.05). In the patients with congestive heart failure, lower body negative pressure also reduced central venous pressure. Baseline plasma atrial natriuretic factor levels were markedly elevated, averaging 438 +/- 138 pg/ml, and decreased to 317 +/- 87 pg/ml at maximal lower body negative pressure (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Blood Pressure; Female; Heart Atria; Heart Failure; Humans; Hypotension; Male; Middle Aged; Norepinephrine; Renin; Vasopressins

We have reported that the renin response to systemic hypotension is inhibited in the presence of elevated atrial pressure and that elevations in atrial pressure of similar or larger magnitude cause graded increases in plasma atrial natriuretic peptide (ANP). Therefore we tested the hypothesis that comparable increments in plasma ANP can inhibit renal hypotension-induced increases in plasma renin activity (PRA) in conscious dogs. Renal perfusion pressure was controlled using cuffs implanted around the abdominal aorta just above the renal arteries. Reducing renal perfusion pressure by 10 or 30% of control caused graded increases in PRA (P less than 0.01). Infusion of 1-28 rat ANP (5 ng X kg-1 X min-1), which increased plasma ANP by 34.8 +/- 7.5 (SE) pg/ml, eliminated increases in PRA in response to a 10% reduction in renal perfusion pressure and markedly inhibited the response to a 30% pressure reduction (P less than 0.01). These results indicate that increments in plasma ANP which reproduce endogenous release inhibit renal hypotension-induced stimulation of PRA. Furthermore, the results provide an explanation for the inhibition of the renin response to renal hypotension during elevated atrial pressure.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Dogs; Hypotension; Kidney Diseases; Renin

The hemodynamic and renal excretory responses to 150-min atriopeptin II (AP II) infusion (330 ng X kg-1 X min-1) were assessed in five chronically instrumented rats with (FR protocol) and without (NR protocol) replaced urinary fluid losses. The observed changes were compared with those obtained by vehicle in the same rats. The hypotension seen with AP II infusion (120-min value: -27 +/- 2%, FR and NR responses combined) was due solely to a decreased cardiac output (CO; 120-min combined value: -34 +/- 3%). Total peripheral resistance remained unchanged or slightly elevated. A drop in stroke volume plus a later-developing (by 75-90 min) decrease in heart rate contributed to the CO decline. This latter bradycardic component, the opposite response to that typically produced reflexly by hypotension, was reversed by atropine sulfate treatment at 120 min and may thus be neural in origin. The finding of similar hemodynamic changes in the FR and NR rats and the lack of a significant effect of AP II on hematocrit suggest that volume depletion or a plasma extravasation were not contributors to the cardioinhibitory effect of the peptide.

Topics: Animals; Atrial Natriuretic Factor; Atropine; Cardiac Output; Heart Rate; Hemodynamics; Hypotension; Kidney; Male; Rats; Rats, Inbred Strains; Time Factors; Vascular Resistance

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Female; Goats; Heart Rate; Hemodynamics; Hemorrhage; Hypotension; Pregnancy; Pregnancy Complications, Cardiovascular; Respiration; Vasopressins

Atrial natriuretic factor (ANF) is released in response to many stimuli which increase right atrial pressure. Following hemorrhage pigs lowered their atrial pressures, developed a tachycardia and increased ANF levels. Electrical pacing increased heart rate and ANF levels. There is a stimulus to ANF release other than atrial stretch, probably heart rate.

Topics: Animals; Atrial Natriuretic Factor; Hemorrhage; Hypotension; Kinetics; Swine; Tachycardia

1. To determine the influence of loss of atrioventricular synchrony on release of atrial natriuretic peptide (ANP), plasma ANP concentrations were measured by radioreceptor assay in 16 patients during sequential and ventricular cardiac pacing at normal heart rates. 2. Ventricular pacing induced an increase in plasma ANP concentrations (means +/- SEM) from 44 +/- 3 to 104 +/- 4 pmol/l (P less than 0.01) in 11 patients in whom systemic blood pressure was maintained. 3. In contrast, when ventricular pacing was associated with a fall in blood pressure (five patients), ANP levels (means +/- SEM) fell from 68 +/- 6 to 14 +/- 4 pmol/l (n = 5, P less than 0.05) within 5 min, despite an increase in atrial pressure. Plasma catecholamines also rose significantly in these latter patients. 4. We conclude that when loss of atrioventricular synchrony is well tolerated haemodynamically, cardiac release of ANP is increased in keeping with elevation in atrial pressure. However, the fall in plasma ANP concentration observed when ventricular pacing produces a fall in blood pressure suggests that in addition to atrial pressure, ANP release may be influenced by negative feedback mechanisms, possibly involving the baroreflex and autonomic nervous system.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Blood Pressure; Catecholamines; Female; Humans; Hypotension; Male; Middle Aged; Pacemaker, Artificial

Chicken artria and ventricles both have membrane-bound granules which resemble those containing atriopeptin (ANP) in mammals. However, nothing is known about the contents of the avian granules. A previous study in chickens showed that although extracts of whole chicken heart or synthetic rat ANP both caused profound hypotension, ANP caused both natriuresis and diuresis, while chicken heart extract did not. The present study sought to locate the region(s) of chicken heart containing the hypotensive activity, and to observe the effect on sodium and water excretion and blood pressure in rats. Acid extracts of either atrium, either ventricle, ventricular septum, skeletal muscle, and liver were identically prepared from chickens and rats. Extracts were adjusted to the same protein concentration and injected (0.15 ml/kg) into anesthetized Single Comb White Leghorn roosters. Mean arterial pressure (MAP) and the time for recovery were measured. The most potent extract from chicken hearts was from the left ventricle (-38 +/- 1 mm Hg, 149 +/- 9 sec to recover). All other extracts (including right ventricle) produced only small (10-20 mm Hg), short-lived (20-30 sec) decreases in MAP. In contrast, only rat atrial extracts evoked long-lasting hypotension (greater than 40 mm Hg, recovery time greater than 200 sec). A 30-min infusion of the most potent chicken extract (left ventricle, CLV) into rats produced a small but significant natriuresis and diuresis compared to the vehicle time control (P less than 0.05) and the hypotensive response to bolus injection was about one-third that seen in the chicken. The location of potent spasmolytic activity primarily in chicken left ventricle, the different avian renal responses to chicken heart extract and synthetic rat ANP (5), and the weak diuretic, natriuretic, and hypotensive effects of CLV extract in rats all suggest that the chicken heart substance may be different from mammalian ANP.

Topics: Animals; Atrial Natriuretic Factor; Chickens; Dose-Response Relationship, Drug; Hypotension; Male; Rats; Rats, Inbred Strains; Sodium; Tissue Extracts; Urodynamics; Ventricular Function

Topics: Acidosis; Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Female; Humans; Hyperkalemia; Hyponatremia; Hypotension; Middle Aged; Oligopeptides; Renin; Teprotide

In order to investigate the relationship between the hypotensive and natriuretic effects of alpha-human atrial natriuretic polypeptide (alpha-hANP) and sodium state, alpha-hANP was chronically administered for 7 days using an osmotic minipump (100 ng/h) to spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) which had been fed either a low- (13.8 mumol/g) or high- (1380 mumol/g) sodium diet. Systolic blood pressure (SBP) and urinary sodium excretion (UNaV) were measured before and during infusion. The SBP in both SHR and WKY fell significantly within 1 day of infusion, and remained reduced for all 7 days, regardless of the sodium intake. The UNaV increased significantly in sodium-replete SHR and WKY compared with rats infused with vehicle, but remained unchanged in sodium-deplete rats. Extracellular fluid volume may be an important determining factor in the natriuretic action of alpha-hANP, but may not affect its hypotensive action.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Consciousness; Hypertension; Hypotension; Natriuresis; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Sodium; Time Factors

The intravenous injection of an ED50 natriuretic dose (1 microgram) of synthetic ANF decreases blood pressure by 61 +/- 6 mmHg in 2-K, 1-C, and of 45 +/- 6 mmHg in 1-K, 1-C hypertensive rats, which was positively correlated with its initial level only in the 2-K, 1-C group. The hypotensive response lasted longer in the latter (greater than 40 min) than in normotensive sham-operated rats. No difference in duration was seen between 1-K, 1-C hypertensive and its uninephrectomized normotensive controls. The diuretic response to ANF was higher in 2-K, 1-C rats. No hematocrit changes were observed in any group. ANF induced a rise in urinary kallikrein in all groups but the 1-K, 1-C. Urinary kallikrein excretion was positively correlated with natriuresis in normotensive but not in hypertensive groups. ANF induced an increase in urinary cGMP excretion in all groups but the 1-K, 1-C, and an increase in plasma cGMP in the normotensive sham-operated animals. Our results suggest that the fall in blood pressure induced by synthetic ANF could be due to vasodilatation, a drop in cardiac output cannot, however, be eliminated. Whether the hypotensive effect of ANF is mediated by cGMP remains to be demonstrated.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Cyclic GMP; Disease Models, Animal; Female; Hypertension, Renovascular; Hypotension; Kallikreins; Nephrectomy; Rats; Rats, Inbred Strains; Time Factors