atrial-natriuretic-factor and Hemorrhage

Coronary heart disease (CHD) is the leading cause of death and disability in Europe. For patients presenting with an acute ST-segment elevation myocardial infarction (STEMI), timely myocardial reperfusion using either thrombolytic therapy or primary percutaneous coronary intervention (PPCI) is the most effective therapy for limiting myocardial infarct (MI) size, preserving left-ventricular systolic function and reducing the onset of heart failure. Despite this, the morbidity and mortality of STEMI patients remain significant, and novel therapeutic interventions are required to improve clinical outcomes in this patient group. Paradoxically, the process of myocardial reperfusion can itself induce cardiomyocyte death-a phenomenon which has been termed 'myocardial reperfusion injury' (RI), the irreversible consequences of which include microvascular obstruction and myocardial infarction. Unfortunately, there is currently no effective therapy for preventing myocardial RI in STEMI patients making it an important residual target for cardioprotection. Previous attempts to translate cardioprotective therapies (antioxidants, calcium-channel blockers, and anti-inflammatory agents) for reducing RI into the clinic, have been unsuccessful. An improved understanding of the pathophysiological mechanisms underlying RI has resulted in the identification of several promising mechanical (ischaemic post-conditioning, remote ischaemic pre-conditioning, therapeutic hypothermia, and hyperoxaemia), and pharmacological (atrial natriuretic peptide, cyclosporin-A, and exenatide) therapeutic strategies, for preventing myocardial RI, many of which have shown promise in initial proof-of-principle clinical studies. In this article, we review the pathophysiology underlying myocardial RI, and highlight the potential therapeutic interventions which may be used in the future to prevent RI and improve clinical outcomes in patients with CHD.

Topics: Animals; Arrhythmias, Cardiac; Atrial Natriuretic Factor; Blood Glucose; Calcium; Cardiotonic Agents; Cell Death; Coronary Occlusion; Disease Models, Animal; Hemorrhage; Humans; Hydrogen-Ion Concentration; Hyperbaric Oxygenation; Hypothermia, Induced; Ischemic Postconditioning; Microvessels; Mitochondria, Heart; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Myocardial Contraction; Myocardial Infarction; Myocardial Reperfusion Injury; Myocarditis; Myocytes, Cardiac; Nitric Oxide; Oxidative Stress; Percutaneous Coronary Intervention

This study was performed to integratively investigate the vasoregulatory response during standardized splanchnic hypoperfusion in pigs. Splanchnic perfusion was reduced to 50% of baseline by: haemorrhage by 20 and 40% of the estimated total blood volume; femoral venous infusion of live E. coli to establish sepsis of systemic origin; portal venous infusion of live E. coli to establish sepsis of splanchnic origin. Invasive haemodynamic monitoring and radioimmunoassay analyses of arterial plasma concentrations of angiotensin II, endothelin-1 and atrial natriuretic peptide were carried out. Acute hypovolaemia reduced systemic and splanchnic vascular resistances following transient increases and increased angiotensin II levels (+587%), whereas endothelin-1 and atrial natriuretic peptide levels did not change significantly. Systemic sepsis following femoral venous infusion of E. coli resulted in increased splanchnic vascular resistance and increased levels of angiotensin II (+274%), endothelin-1 (+134%) and atrial natriuretic peptide (+185%). Infusion of E. coli via the portal venous route induced an increase in splanchnic vascular resistance associated with particularly elevated levels of angiotensin II (+1770%) as well as increased endothelin-1 (+201%) and atrial natriuretic peptide (+229%) concentrations. Hypovolaemia and sepsis, although standardized with a predefined level of splanchnic hypoperfusion, elicited differentiated cardiovascular and vasopeptidergic responses. Sepsis, particularly of portal origin, notably increased splanchnic vascular resistance related to increased production of the vasoconstrictors angiotensin II and endothelin-1. The role of atrial natriuretic peptide as a vasodilator seems to be of subordinate importance in hypovolaemia and sepsis.

Topics: Acute Disease; Anesthesia; Angiotensin II; Animals; Atrial Natriuretic Factor; Endothelin-1; Escherichia coli Infections; Female; Femoral Vein; Hemorrhage; Hypovolemia; Male; Neuropeptides; Portal Vein; Sepsis; Splanchnic Circulation; Swine; Vasoconstrictor Agents

The effect of intracerebroventricular infusions of C-type natriuretic peptide (CNP-22, 5 micrograms/h for 3 h) or vehicle on the neurohumoral response of conscious sheep (n = 7) to acute moderate hemorrhage (15 ml/kg in 15 min performed 1 h after start of CNP) was studied. CNP alone (prehemorrhage) induced a transient rise (after 30 min) in heart rate (p = 0.0005), plasma aldosterone (p = 0.007), ACTH (p = 0.049), and cortisol (p = 0.049), with values returning to control levels immediately prehemorrhage. Hemorrhage caused arterial pressure to fall (15 mmHg) and heart rate to rise similarly on both study days. Compared with vehicle, posthemorrhage responses of AVP (p = 0.05) and cortisol (p = 0.004) were greater during CNP. Thus, central CNP-22 augmented the hypothalamic-pituitary-adrenal axis at baseline and in response to hemorrhage in conscious sheep.

Topics: Animals; Atrial Natriuretic Factor; Female; Hemorrhage; Injections, Intraventricular; Natriuretic Peptide, C-Type; Neurotransmitter Agents; Proteins; Sheep

1. Early research on blood volume as an independent parameter affecting kidney function took the approach that the sensors must be located in the most compliant, that is the reservoir portion, of the cardiovascular system. This encompasses the great veins and the cardiac atria. 2. Small changes in volume were shown not to affect the compliance of this reservoir and messages from the atrial receptor network were shown to travel in the vagus nerve and to control urine volume by antidiuretic hormone. 3. Although greatly affected by the water immersion stimulus, sodium excretion was not as dependent on vagus integrity. The ensuing search for the natriuretic arm of the blood volume mechanism persisted for the next 20 years. 4. Finally, one aspect of the elusive natriuretic factor was found exactly where theory had suggested, namely the most distensible part of the system, in specialized granules in the cardiac atria.

Topics: Animals; Atrial Function; Atrial Natriuretic Factor; Blood Pressure; Blood Volume; Dogs; Heart; Heart Atria; Hemorrhage; History, 20th Century; Humans; Kidney; Physiology; Urination

Hemorrhage induces a rapid redistribution of protein from extravascular spaces into the blood. We studied the effects of acute, nontraumatic hemorrhage on tracer-albumin clearances into individual tissues of rats to determine if reduced protein extravasation could account for intravascular protein gain. Three groups were studied: 1) HEM animals were anesthetized with pentobarbital sodium and bled to a mean arterial pressure of 50 mmHg for 90 min; 2) HEM-RS animals were treated identical to group 1 and then resuscitated with 5% bovine serum albumin (BSA) until baseline arterial pressures were regained; 3) SHAM animals served as time controls. Hemodynamic variables were measured periodically throughout hemorrhage and clearance periods, and plasma samples were collected prior to death for protein and hormone analysis. Plasma clearance of 131I-BSA into individual tissues was measured over the final 30 min of each protocol with a terminal injection of 125I-BSA used to correct for intravascular volume. Reduction of blood volume by 35% in HEM-treated animals resulted in a marked decrease in albumin transport relative to the SHAM group (p < or = .05) in the following tissues: skeletal muscle (-65%), skin (-49%), ileum (-75%), cecum (-66%), colon (-67%), heart (-67%), and lung (-71%). Significant changes were not observed in the remaining tissues sampled: pancreas, kidney, and cerebrum. Albumin clearances in the HEM-RS group were slightly but not significantly lower than SHAM animals except for skeletal muscle, where transport remained depressed following resuscitation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Animals; Atrial Natriuretic Factor; Biological Transport; Blood Glucose; Blood Volume; Body Water; Body Weight; Brain; Colon; Coronary Vessels; Disease Models, Animal; Extravascular Lung Water; Hematocrit; Hemodynamics; Hemorrhage; Ileum; Lung; Male; Osmolar Concentration; Plasma Volume; Rats; Rats, Wistar; Resuscitation; Serum Albumin; Skin; Tissue Distribution; Vasopressins

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

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

We examined the effect of hemorrhage on plasma NH2-terminal pro-atrial natriuretic peptide (NT-pro-ANP) and atrial natriuretic peptide (ANP) in anesthetized and conscious rats. Blood (1.5 ml/time point) was withdrawn at 0, 10, 20, and 30 min. In anesthetized rats it caused decrease in mean arterial pressure and led to bradycardia in 2 min. Right atrial pressure decreased significantly after 12 min. However, plasma ANP did not change, and NT-pro-ANP actually increased from 481 +/- 55 to 609 +/- 73 pmol/l (P < 0.01) at 20 min and to 696 +/- 82 pmol/l (P < 0.01) at 30 min. Also plasma arginine-8-vasopressin (AVP) and epinephrine increased significantly at 30 min. No significant changes in plasma endothelin and norepinephrine were found. The increase in NT-pro-ANP after hemorrhage was not blocked by AVP V1-receptor, alpha- and beta-catecholaminergic receptor, or muscarinic-receptor antagonists. The plasma 125I-ANP disappearance curve was shifted to the right after hemorrhage in anesthetized rats, suggesting that the elimination of ANP was decreased. In conscious rats, heart rate and right atrial pressure did not change significantly after hemorrhage, and mean arterial pressure did not decrease until 22 min. NT-pro-ANP decreased from 1,467 +/- 146 to 1,072 +/- 130 pmol/l (P < 0.01) at 20 min and to 941 +/- 41 pmol/l (P < 0.01) at 30 min. Plasma ANP did not respond to hemorrhage in conscious rats. In conclusion, we found no change in plasma ANP during hemorrhage in either anesthetized or conscious rats, but we did find a significant increase in plasma NT-pro-ANP levels in anesthetized rats and a significant decrease in conscious rats. We suggest that this divergence may be due to different hemodynamic responses to hemorrhage.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Atrial Natriuretic Factor; Atropine; Blood Pressure; Cardiovascular System; Hemorrhage; Hormones; Male; Protein Precursors; Rats; Rats, Sprague-Dawley; Sympatholytics

Whether intracerebroventricular (i.c.v.) infusion of atrial natriuretic peptide (human-ANP, 1-28) 25 pmol min-1 influences the tolerance to blood loss and haemorrhage induced cardiovascular, vasopressin and renin responses were studied in five conscious sheep. The i.c.v. infusion was started 60 min prior to a slow (0.7 ml kg-1 min-1) venous haemorrhage, was run concurrently with bleeding, and for 90 min thereafter. Venous blood was removed until the mean systemic arterial pressure suddenly fell to about 50 mmHg. There were no statistically significant differences in either the bleeding volume necessary to induce the sudden decrease in blood pressure, or in cardiovascular parameters measured by venous heart thermodilution catheterization, compared with control experiments with i.c.v. infusion of artificial CSF. The plasma protein and vasopressin concentrations and renin activity were unaffected by the i.c.v. infusion of ANP as were the changes in these parameters occurring during the subsequent haemorrhage. The same negative findings were obtained with a three times higher dose of ANP(1-28) (75 pmol min-1), tested in three of the animals. Thus the i.c.v. infusion of ANP(1-28), in amounts expected to elevate the CSF concentration far above basal levels does apparently not influence normal blood pressure regulation or alter haemodynamic, vasopressin and renin responses to haemorrhage in conscious sheep.

Topics: Animals; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Proteins; Brain; Female; Hemodynamics; Hemorrhage; Injections, Intraventricular; Renin; Sheep

The effects of alpha-hANP (0.3 micrograms/kg body weight/min) on the baroreflex system were studied in anesthetized dogs according to three different protocols. In the first protocol, the effects of alpha-hANP on an open-loop gain (G(AP)) of the overall baroreflex system and a gain (GHR) of the baroreflex heart rate control system during quick mild hemorrhage and blood infusion were studied. G(AP) was decreased from 7.6 +/- 0.6 to 2.8 +/- 0.5 by alpha-hANP with hemorrhage. G(AP) decreased 7.4 +/- 0.8 to 2.9 +/- 0.4 by alpha-hANP with blood infusion. G(AP) was restored nearly to the control levels one hour after alpha-hANP administration. GHR did not change by alpha-hANP administration. In the second and third protocol, a site of action of alpha-hANP was analysed. alpha-hANP inhibited the responses of systemic vascular resistance to quick mild hemorrhage and blood infusion, but did not affect the responses of cardiac output to quick mild hemorrhage and blood infusion in the second protocol. After carotid sinus denervation and vagotomy, alpha-hANP inhibited an arterial pressure responses to phenylephrine and nitroglycerin bolus injection in the third protocol. These findings suggest that alpha-hANP has mainly an effect on the peripheral vascular system to decrease its responsiveness, resulting in a decrease in G(AP).

Topics: Anesthesia; Animals; Atrial Natriuretic Factor; Blood Pressure; Blood Transfusion; Cardiac Output; Carotid Sinus; Dogs; Heart Rate; Hemorrhage; Pressoreceptors; Vagus Nerve; Vascular Resistance

Intracerebroventricular hANP (50 nmol) inhibits release of vasopressin and oxytocin following dehydration as well as after haemorrhage. 10 nmol/L hANP markedly inhibits vasopressin and oxytocin release in vitro from the neurointermediate lobes both under basal condition as well as during stimulation with excess (56 mM) potassium. It is suggested that ANP may serve as a modulator of vasopressin and oxytocin release. The respective processes are localized, at least in part, at the neurohypophysial level.

Topics: Animals; Atrial Natriuretic Factor; Dehydration; Femoral Vein; Hemorrhage; Injections, Intraventricular; Male; Oxytocin; Pituitary Gland, Posterior; Pituitary Hormones, Posterior; Potassium; Rats; Rats, Wistar; Vasopressins

ANP administered to cirrhotic dogs or chronic caval dogs with ascites and urinary sodium retention (USR) usually causes heterogeneity of natriuretic response. To assess whether this same phenomenon would occur in the absence of edema, ANP at 100 ng/kg/min was given to dogs before and after the induction of USR by a variety of techniques. Eight dogs were over-diuresed with furosemide over a 2-day period, and 9 dogs were subjected to subacute hemorrhage over a similar period. These dogs were retested with ANP one day later. All 8 dogs given furosemide showed no response to ANP (delta UNa V = 7.4 +/- 4.8 microEq/min), compared to a normal response prior to the diuretic (delta UNa V = 128 +/- 34 microEq/min). The 9 hemorrhaged dogs also responded normally to ANP prior to this manipulation (delta UNa V = 74 +/- 14 microEq/min), but a blunted response post-hemorrhage (delta UNa V = 35 +/- 13 microEq/min). This profile was made up of 5 dogs who responded to ANP (delta UNaV = 62 microEq/min) and 4 who had no response whatsoever (delta UNa V = 3 microEq/min). When 8 dogs were given USR because of continuous mineralocorticoid administration, none responded, but all had a magnified natriuretic response to ANP during the 'escape' phase. Eight dogs were administered minoxidil (10 mg) by mouth daily to induce USR. All 8 dogs responded to ANP (delta UNa V = 93 +/- 6 microEq/min) which was no different from the pretreatment response (delta UNa V = 65 +/- 3 microEq/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atrial Natriuretic Factor; Dogs; Edema; Female; Fludrocortisone; Furosemide; Glomerular Filtration Rate; Hemorrhage; Kidney Diseases; Male; Minoxidil; Natriuresis

The aim was to measure changes in atrial wall function over a wide range of atrial filling pressures in order to determine the relationship governing the atrial stretch in vivo.. Acute graded haemorrhage, 30 ml.kg-1, was used to reduce atrial stretch, and volume loading with 1000 ml saline was used to increase atrial stretch.. Awake mongrel dogs (n = 6) were instrumented for the measurement of left atrial appendage pressure and diameter; awake mongrel dogs (n = 4) were instrumented for measurement of left and right atrial appendage pressures and diameters.. During haemorrhage, left atrial pressure and diameter decreased progressively, and plasma atrial natriuretic factor fell from 44 (SEM 10) to 25(5) pg.ml-1 (p less than 0.05). Calculated left atrial wall stress and minute wall stress fell by 80(5.8)% and 72(15)% (p less than 0.05 from control). During volume expansion, however, atrial wall stress and minute wall stress markedly increased and plasma atrial natriuretic factor increased by more than 500%. The relationship between left atrial pressure and diameter was a typical exponential compliance curve during volume loading and haemorrhage for atrial systole, the A wave, and for atrial diastole, the V wave. During volume expansion right atrial pressure and diameter were also related exponentially. Left atrial passive stretch, as measured by V wave wall stress, increased more than right atrial stretch during volume loading. Changes in atrial filling in conscious dogs therefore result in typical exponential changes in atrial pressure and diameter in both atria. Plasma atrial natriuretic factor only increased at high filling pressures. The relationship between passive V wave minute wall stress and plasma atrial natriuretic factor also fitted an exponential curve. Thus when atrial filling was reduced, plasma atrial natriuretic factor fell by only 50% from control, while when atrial filling increased over the physiological range (up to 15 mm Hg left atrial pressure), it rose only to 100 pg.ml-1.. Very high atrial appendage wall stresses are required to increase plasma atrial natriuretic factor markedly. Atrial stretch and the release of atrial natriuretic factor are non-linearly related. The stimulus for atrial natriuretic factor release is related to the exponential changes in atrial function due to the underlying atrial compliance relationship.

Topics: Animals; Atrial Function; Atrial Natriuretic Factor; Blood Volume; Dogs; Hemorrhage

To assess the effect of cardiopulmonary denervation on the release of arginine vasopressin (AVP) and atrial natriuretic peptide (ANP), either hemorrhage (1.0 ml.kg-1.min-1, for 40 min) or an infusion of 3% dextran in lactated Ringer solution (RL) (3% dextran in RL, 1.0 ml.kg-1.min-1, for 40 min) was carried out in chronic cardiopulmonary denervated (CPD, n = 7) and sham-operated (SO, n = 7) dogs under anesthesia. Plasma AVP increased significantly in both groups during hemorrhage, but its rise was significantly attenuated in CPD dogs. Plasma ANP decreased similarly during hemorrhage in both groups. An infusion of 3% dextran in RL decreased significantly plasma AVP during its whole period in SO dogs, but AVP release was only suppressed in the late period in SO dogs. Plasma ANP increased significantly during its infusion in both groups. These results indicate that cardiopulmonary denervation may attenuate the release of AVP in response to either hemorrhage or blood volume expansion but may not affect the release of ANP in response to the blood volume change. Moreover, a large increase in plasma ANP may attenuate the release of AVP.

Topics: Animals; Arginine Vasopressin; Atrial Natriuretic Factor; Denervation; Dextrans; Dogs; Heart Conduction System; Hemodynamics; Hemorrhage; Infusions, Intravenous; Lung; Nervous System Physiological Phenomena

This study was designed to investigate whether an infusion of atrial peptide is capable of modulating the hormonal and hemodynamic responses elicited by acute hemorrhage. Conscious dogs were bled at a rate of 0.8 ml.kg-1.min-1 until 20 ml of blood/kg body wt had been removed. Two experiments were performed on each dog; in one experiment the animal was given alpha-human atrial natriuretic peptide (alpha-hANP) (50 ng.kg-1.min-1) dissolved in saline; in the other only the saline vehicle was given. Right and left atrial pressures decreased during hemorrhage in all experiments; the absolute decreases were greater when the animals received atriopeptin, but the differences between treatments were statistically significant only for right atrial pressure. Cardiac output decreased (P less than 0.05) and total peripheral resistance increased (P less than 0.05) during hemorrhage when atriopeptin was infused; although these variables showed similar trends when vehicle alone was infused during hemorrhage, no significant changes occurred. Infusion of atrial peptide did not affect the decrease in arterial blood pressure that occurred during hemorrhage. The increase in plasma vasopressin induced by hemorrhage was potentiated, but the increase in plasma renin activity was attenuated when alpha-hANP was infused. Hemorrhage increased circulating aldosterone levels in each experiment, but the response was less pronounced when alpha-hANP was given during the experiment. Intravenous administration of alpha-hANP modulates the hemodynamic responses elicited by hemorrhage, potentiates the rise in plasma vasopressin, and attenuates the rise in plasma renin activity induced by acute blood loss in conscious dogs.

Topics: Aldosterone; Animals; Atrial Natriuretic Factor; Blood Pressure; Cardiac Output; Dogs; Epinephrine; Female; Hematocrit; Hemorrhage; Osmolar Concentration; Potassium; Renin; Sodium; Vascular Resistance; Vasopressins

The central actions of atrial natriuretic peptide (ANP) in rats include inhibition of arginine vasopressin (AVP) release, and less consistently, ACTH suppression and hypotension. To explore any such inhibitory actions on basal and stimulated levels of AVP and ACTH, we have studied the effect of intracerebroventricular (ICV) infusion of ANP on the hemodynamic and hormonal response to acute hemorrhage in conscious sheep. Two groups of 5 sheep received rat ANP(101-126) by ICV infusion (0.5 microgram bolus followed by 0.5 microgram/h for 3 h, or 5 micrograms bolus followed by 5 micrograms/h for 3 h) as well as artificial cerebrospinal fluid control infusions in random order. One hour after the start of the ICV infusion, acute hemorrhage (15 ml/kg BW within 10 min) was performed. Basal levels before hemorrhage of mean arterial pressure (MAP), heart rate and plasma hormones were unaltered by either dose of ICV ANP. After hemorrhage, the fall in MAP and rise in heart rate were similar in each group. However, compared to control infusions the response to hemorrhage of ACTH (433 +/- 147 to 2,175 +/- 588 vs. control 541 +/- 103 to 893 +/- 244 ng/l; p less than 0.016) and angiotensin II (AII) (18 +/- 3 to 94 +/- 23 vs. control 18 +/- 4 to 58 +/- 8 pmol/l; p less than 0.001) were significantly greater during high-dose ANP infusion. Although peak AVP levels more than doubled those observed on the control day, the increase did not reach statistical significance (p less than 0.1053). Plasma concentration of cortisol, aldosterone, epinephrine and norepinephrine were not significantly different in control and ANP-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenocorticotropic Hormone; Angiotensin II; Animals; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Cerebral Ventricles; Female; Heart Rate; Hemorrhage; Kinetics; Sheep

The ability of atrial natriuretic peptide (ANP) to preserve renal function in dogs with hypovolemic acute renal insufficiency was tested in anesthetized dogs 4 h after the induction of acute pancreatitis. Plasma volume had decreased by 21.5% and glomerular filtration rate (GFR) by 43.2%. Blood pressure had declined by 30 mmHg. ANP was given intravenously at 50 and 150 ng.kg-1.min-1. With the lower dose, blood pressure (BP), GFR, and clearance of p-aminohippuric acid (CPAH) did not change but urine flow (V) and sodium excretion (UNaV) increased. With the higher dose, BP declined by 25 mmHg, GFR declined, but V and UNaV still increased. When plasma volume was maintained with 4% colloid during the progression of pancreatitis and ANP 50 ng.kg-1.min-1 given, BP declined, GFR did not change, and there was a magnified increment in V and UNaV. The administration of glucagon (5 micrograms/min iv) to dogs with hypovolemic pancreatitis caused BP to decline by 17 mmHg. Despite a major increment in GFR, fractional excretion of sodium increased only slightly, compared with that obtained with ANP. We conclude that glucagon preserves GFR more effectively than ANP in hypovolemia, but ANP is more effective in protecting urinary water and sodium excretion.

Topics: Acute Disease; Acute Kidney Injury; Animals; Atrial Natriuretic Factor; Dogs; Female; Glomerular Filtration Rate; Glucagon; Hemorrhage; Kidney; Male; Pancreatitis; Plasma Volume; Shock

Hemorrhage of 14 ml/kg in 5 min was done in two groups of chronically prepared, splenectomized Yorkshire pigs. Group 1 was studied on post-operative day 4 and was conditioned behaviorally with "active restraint", whereas group 2 was studied on postoperative day 6 and was conditioned with behavioral "shaping." The peak decrease in blood volume occurred by 0.25 h after hemorrhage in both groups. However, plasma atrial natriuretic factor (ANF) as measured by radioimmunoassay did not decrease significantly until 2 h in group 1 and 0.5 h in group 2 even though the recovery of blood volume was significantly more rapid in group 1 than in group 2. The responses of ANF differed significantly between groups, suggesting that ANF release after hemorrhage is influenced by prior handling and the time for recovery from surgery. In both groups, some pigs showed increases in ANF during the 1st h after hemorrhage, and changes in ANF were unrelated to decreases in central venous pressure or absolute right atrial volume determined with a conductance catheter. In contrast, changes in ANF after hemorrhage correlated positively with several variables including atrial rate and changes in vasopressin. Multiple regression suggested that the effect of reduced atrial volume on ANF release was opposed by these latter variables or related factors. Furthermore, known actions of ANF do not appear to account for the observed hemodynamic and hormonal responses to hemorrhage.

Topics: Animals; Atrial Natriuretic Factor; Blood Volume; Cardiac Pacing, Artificial; Conditioning, Psychological; Female; Heart Rate; Hemorrhage; Swine

The influence of aortic baroreceptors and vagal afferent nerves on the release of immunoreactive vasopressin (iVP) and immunoreactive atrial natriuretic factor (iANF) was examined in anaesthetized rabbits. Changes in plasma concentrations of iVP and iANF, heart rate, mean arterial pressure, and right atrial pressure were measured in response to blood volume changes (+20, +10, -10, -20%). Carotid sinus pressure was maintained at 100 mmHg (1 mmHg = 133.3 Pa), and blood volume changes were performed before and after bilateral vagotomy (VNX) in all experiments. Two experimental groups were studied: rabbits with aortic depressor nerves intact (ADNI) and those with aortic depressor nerves sectioned (ADNX). Mean arterial and right atrial pressures decreased during haemorrhage and increased in response to volume expansion. Plasma iVP concentrations increased with haemorrhage and decreased with volume expansion in the ADNI group. Plasma iANF, however, decreased with haemorrhage and increased during volume expansion in both ADNI and ADNX groups. Vagotomy caused an increase in baseline plasma iANF in the ADNX group. The responses of iANF to blood volume changes were augmented after VNX and ADNX. The results show that neither the aortic baroreceptor nor the vagal afferent input are needed for the iANF response to changes in blood volume, over the range of +/- 20%. In contrast, intact aortic baroreceptors are essential for changes in circulating iVP in this preparation.

Topics: Animals; Aorta; Atrial Natriuretic Factor; Blood Pressure; Blood Volume; Hemorrhage; Rabbits; Radioimmunoassay; Reference Values; Vasopressins

These experiments investigated the change in brain, atrial, and plasma concentrations of atrial natriuretic polypeptide (ANP) after a 33% hemorrhage and the role of vagal nerve input in these changes. In rats, hemorrhage decreased plasma ANP from 246 +/- 48 to 41 +/- 7 pg/ml, but in a hypothalamic tissue block ANP increased from 19.0 +/- 0.9 to 25.5 +/- 0.6 ng/g tissue (P less than 0.05). Bilateral vagotomy was followed by a very large increase in plasma ANP to 703 +/- 198 pg/ml. Atrial pressures, however, fell after vagotomy from 2 +/- 2 to 1 +/- 1 mmHg. Therefore, the effect was not due to increased atrial stretch. Right atrial ANP levels were also elevated by vagotomy, but left atrial ANP concentrations did not change with vagotomy or hemorrhage. After hemorrhage in vagotomized rats, plasma ANP decreased to 79 +/- 6 pg/ml. After vagotomy, the ANP concentration in the hypothalamic block did not rise in response to hemorrhage. The results indicate that the vagus nerves provide a tonic inhibition of ANP levels in atria and plasma. The results cannot be explained by atrial distension. The results show independence of brain and plasma ANP and uncover a tonic vagal inhibition of ANP release.

Topics: Animals; Atrial Natriuretic Factor; Heart Atria; Hemorrhage; Hypothalamus; Myocardium; Radioimmunoassay; Rats; Rats, Inbred Strains; Reference Values; Vagotomy; Vagus Nerve

1. The changes in plasma concentrations of immunoreactive vasopressin (iVP) and atrial natriuretic factor (iANF) in response to haemorrhage (10-30% blood volume) were measured in 10 anaesthetized rabbits before and after cardiac receptor denervation (vagal nerve section). Carotid sinus pressure was maintained constant (60 mmHg) to eliminate any changing input from carotid baroreceptors. 2. Haemorrhage increased iVP before and after vagal nerve section indicating that withdrawal of input from aortic baroreceptors may have contributed to the increase in iVP. 3. Section of the vagus nerves attenuated the iVP response to haemorrhage. 4. There was no correlation between release of iVP and iANF. 5. Haemorrhage decreased iAF before and after vagal nerve section. Section of the vagus nerves increased iANF. Plasma iANF was highly correlated with atrial pressure and mean arterial pressure suggesting iANF release was secondary to changes in cardiac haemodynamics.

Topics: Animals; Aorta, Thoracic; Atrial Natriuretic Factor; Blood Pressure; Blood Volume; Heart Rate; Hemorrhage; Male; Myocardium; Rabbits; Radioimmunoassay; Receptors, Cell Surface; Time Factors; Vasopressins

The effect of rat atrial natriuretic peptide (ANP) on basal hemodynamic and hormonal function and on the response to acute hemorrhage was studied in eight conscious sheep. ANP infusions (3 micrograms/kg BW bolus, followed by 50 ng/kg.min for 70 min) increased plasma immunoreactive ANP levels from less than 12 pmol/liter to steady state levels of 523 +/- 20 pmol/liter, reduced arterial pressure by 14% (P less than 0.002), increased heart rate by 26% (P less than 0.06), and increased plasma norepinephrine levels (P less than 0.015) compared to control values. These changes were associated with a significant increase in plasma cortisol (P less than 0.05) and smaller increases in plasma ACTH and arginine vasopressin (AVP), but plasma angiotensin II (AII) and aldosterone were unaffected. When hemorrhage (15 ml/kg BW over 10 min) was performed during ANP or control infusions, hypotension was greater (P less than 0.0004) during ANP treatment and the responses of plasma ACTH, AVP, catecholamines, and AII were enhanced compared with those to control hemorrhage. Plasma immunoreactive ANP during ANP infusions was significantly higher after hemorrhage (mean, 833 +/- 46; P less than 0.003), but the disappearance rate after the termination of ANP infusion was the same (3.1 min) with or without hemorrhage. These studies show that ANP infusions, achieving plasma levels observed in pathological states such as congestive heart failure, inhibit the expected responses of plasma AII and aldosterone to mild acute hypotension, but do not inhibit the responses of plasma AVP, ACTH, AII, and aldosterone associated with acute moderate hemorrhage in conscious sheep.

Topics: Adrenocorticotropic Hormone; Aldosterone; Angiotensin II; Animals; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Female; Heart Rate; Hemodynamics; Hemorrhage; Hormones; Hydrocortisone; Norepinephrine; Sheep

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

An increase in atrial pressure has been shown to cause an increase in the concentration of atrial peptides (atriopeptin) in plasma. We therefore hypothesized that a reduction in atrial pressure would decrease the concentration of atriopeptin in plasma. In formulating this hypothesis we assumed that changes in the concentration of other circulating hormones or changes in cardiac nerve activity during hemorrhage would not affect the secretion of atriopeptin. To test the hypothesis, we bled sham-operated conscious dogs at a rate of 0.8 ml.kg-1.min-1 to decrease right and left atrial pressures. Hemorrhage was continued until a total of 30 ml of blood per kilogram body weight had been removed. Identical experiments were performed on conscious cardiac-denervated dogs. The concentration of plasma atriopeptin was decreased in each group of dogs after 10 ml of blood per kilogram of body weight had been removed, but the decrease achieved statistical significance only in the cardiac-denervated dogs. Further hemorrhage, however, produced no further decreases in circulating atriopeptin in either group even though atrial pressures continued to decline as more blood was removed. A comparison of the atriopeptin response to hemorrhage revealed no significant difference between the sham-operated and cardiac-denervated dogs, thus providing no evidence for a specific effect of cardiac nerves on atriopeptin secretion during hemorrhage. Our results demonstrate that the relationship between atrial pressure and plasma atriopeptin that has been observed repeatedly during atrial stretch is not evident during relatively slow, prolonged hemorrhage. There is, however, a small decline in circulating atriopeptin during the initial stage of hemorrhage that could be of biological significance.

Topics: Animals; Atrial Natriuretic Factor; Dogs; Female; Hematocrit; Hemodynamics; Hemorrhage; Osmolar Concentration; Potassium; Time Factors; Vasopressins

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

This study investigated whether excision of either the right or left atrial appendage of rats alters their natriuretic response and the release of atrial natriuretic factor during acute blood volume expansion or reduction. These animals were subjected to a thoracotomy and either had their right or left atrial appendages removed or underwent a right or left atrial sham appendectomy for comparative, control purposes. Intrajugular vein, intracarotid artery, and intravesical catheters were installed 3-4 weeks later under sodium pentobarbital anesthesia. Then, when the rats were conscious, blood volume was expanded using blood from donor rats once every 15 minutes in 3 increments of 10% of the calculated total blood volume at a rate of 5 ml/kg/min. Blood and urine samples were collected before volume expansion and at the end of each 15-minute period, with the withdrawn blood being replaced. A maximal fourfold increase in urinary volume, urinary sodium excretion, and plasma atrial natriuretic factor was observed in all but the right-atrial-appendectomized animals. Plasma atrial natriuretic factor, urinary volume, and urinary sodium excretion were correlated in all 4 groups. No significant changes in blood pressure or hematocrit were noted. Plasma vasopressin, measured at the end of volume expansion, was significantly lower in animals subjected to left atrial appendectomy. High-performance liquid chromatography of plasma from the control groups indicated that most of the released ANF during blood volume expansion corresponded to a high molecular weight peptide. Additional rats, processed as above, were subjected to 10% blood volume decrements.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atrial Function; Atrial Natriuretic Factor; Blood Pressure; Blood Transfusion; Blood Volume; Disease Models, Animal; Heart Atria; Hemorrhage; Hypertension; Male; Natriuresis; Rats; Rats, Inbred Strains; Sodium; Urodynamics; 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. Plasma concentrations of atrial natriuretic peptide (ANP) and antidiuretic hormone (ADH) were measured in conscious stroke-prone spontaneously hypertensive (SPR), spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats before and after acute volume expansion or haemorrhage. 2. Plasma ANP concentration was reduced to one-third of resting values 30 min after a 1.5% haemorrhage (1.5 ml of blood per 100 g bodyweight). Plasma ADH concentration rose immediately 50-fold on haemorrhage and remained elevated at 30 min. 3. Plasma ANP concentration increased 2.5-fold relative to resting values 1 min after infusion of 2.0 ml per 100 g 5% dextrose; after 10 min plasma ANP remained elevated. Plasma ADH concentration tended to fall on volume expansion although no significant decrease was observed. 4. There was no difference in the basal levels of ANP and ADH, or in the changes produced by alterations in blood volume, in hypertensive SPR and SHR compared with normotensive WKY. 5. Thus, plasma ANP concentrations moved in opposite directions in response to two physiological stimuli: volume expansion and haemorrhage. Reciprocal changes were observed in plasma ADH.

Topics: Animals; Atrial Natriuretic Factor; Blood Volume; Hemorrhage; Hypertension; Male; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Rats, Inbred WKY; Vasopressins

Low-pressure atrial baroreceptors are important in the regulation of plasma volume. Plasma atrial natriuretic factor (ANF) increases with volume loading, and may therefore be influenced by manoeuvres which affect venous return and right atrial pressure. Plasma ANF was measured in six normal subjects following head-up and head-down tilt, changes in posture, severe exercise and haemorrhage. Plasma ANF concentrations were similar while the subjects were supine, sitting, standing or tilted head-up. Plasma ANF rose from 6.9 +/- 0.8 pmol/l while supine to 11.8 +/- 1.9 pmol/l while tilted head-down (P less than 0.05) and to 27.2 +/- 1.3 pmol/l following severe exercise (P less than 0.05). There was no significant change in plasma ANF following haemorrhage of up to 1000 ml. The effects of posture and blood loss are small, and may be largely discounted when blood is drawn for measurement of plasma ANF concentration in normal man. Our results suggest that in normal man the basal secretion of ANF is low, and is not further suppressed by manoeuvres which decrease the right atrial pressure or volume. In contrast, manoeuvres which increase the right atrial pressure or volume are associated with a rapid increase in ANF release from the heart.

Topics: Adolescent; Adult; Atrial Natriuretic Factor; Hemorrhage; Humans; Male; Physical Exertion; Posture

The effect of synthetic alpha-human atrial natriuretic polypeptide (alpha-hANP) on the in vivo and in vitro release of ACTH and corticosterone was examined. In the in vivo study ACTH and corticosterone responses to rapid 2-ml/rat hemorrhage were measured in sixteen conscious rats after alpha-hANP administration. The hemorrhage increased plasma ACTH and corticosterone concentrations in the control group of rats (p greater than 0.01). ANP inhibited hemorrhage-induced ACTH secretion (p less than 0.05), but the plasma corticosterone response was not affected. In the in vitro study a high concentration of ANP (1 microM) reduced basal corticosterone secretion from the isolated rat adrenal gland (p less than 0.05), but the response to ACTH (10 ng/ml) and dibutyryl cyclic AMP (0.5 mM, 5.0 mM) was not affected. Our data suggest that ANP inhibits hemorrhage-induced ACTH secretion from the anterior pituitary but inhibits corticosterone secretion from the adrenal gland very weakly.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; Atrial Natriuretic Factor; Corticosterone; Cyclic AMP; Hemorrhage; In Vitro Techniques; Male; Rats; Rats, Inbred Strains

Peptides of cardiac origin, termed atrial natriuretic factors, possess both natriuretic and diuretic properties, actions which physiologically contradict those of the antidiuretic peptide, arginine vasopressin (AVP). In addition to their opposing actions in the kidney, the present results indicate that one of these factors, Atriopeptin III, can inhibit dehydration and hemorrhage-induced AVP release in the rat. 3 days of water deprivation resulted in elevated plasma AVP levels (36.1 +/- 4.7 pg AVP/ml) which were significantly reduced following intravenous infusion of 0.02 (21.4 +/- 3.6), 0.2 (15.6 +/- 1.6), and 2.0 (13.9 +/- 3.8) nmol Atriopeptin III. Furthermore, 2.0 nmol Atriopeptin III significantly reduced post-hemorrhage levels (54.8 +/- 13.7) of AVP to values that approximated resting levels (10.2 +/- 3.7). The results suggest a role for cardiac peptides in the control of AVP release as well as the existence of a counterregulatory system, peptidergic in nature, for the maintenance of fluid and electrolyte homeostasis.

Topics: Animals; Arginine Vasopressin; Atrial Natriuretic Factor; Dehydration; Hemorrhage; Male; Muscle Proteins; Pituitary Gland, Posterior; Rats; Rats, Inbred Strains