atrial-natriuretic-factor and Renal-Insufficiency

Congestion represents the primary reason for hospitalization of patients with heart failure and is associated with adverse outcomes. Fluid overload has been shown to be inadequately addressed in a significant subset of these patients in part due to lack of robust, reliable, and readily available biomarkers for objective assessment and monitoring of therapy. Natriuretic peptides have long been used in this setting, often in conjunction with other assessment tools such as imaging studies. Patients presenting with concomitant cardiac and renal dysfunction represent a unique population with regard to congestion in that the interactions between the heart and the kidney can affect the utility and performance of biomarkers of fluid overload. Herein, we provide an overview of the currently available evidence on the utility of natriuretic peptides in these patients and discuss the clinical conundrum associated with their use in the setting of renal dysfunction. We highlight the potential divergence in the role of natriuretic peptides for assessment of volume status in a subset of patients with renal dysfunction who receive renal replacement therapy and call for future research to elucidate the utility of the biomarkers in this setting.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Female; Heart Failure; Humans; Kidney; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Prognosis; Renal Insufficiency; Renal Replacement Therapy

Several studies indicated that B-type natriuretic peptide (BNP) assay is able to detect patients even in the early phases of heart failure (HF), when the myocardial remodeling process may be still reversible. BNP assay may assist the physician to initiate appropriate and prompt pharmacological treatments. However, clinical relevance and result interpretation of BNP assay for the guide of therapy or in particular clinical conditions, such as renal failure or treatment with inhibitors of enzymes degrading BNP in HF patients, are still debated. The aim of this article is to discuss some still controversial issues concerning the clinical use of measurement of cardiac natriuretic peptides, and also to provide a general overview and some perspectives related to pathophysiological mechanisms of HF.

Topics: Atrial Natriuretic Factor; Biomarkers; Forecasting; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Renal Insufficiency

In the last three decades many members of the natriuretic peptide family was isolated. The function and physiological role of these peptides are pleiotropic. All natriuretic peptides are synthesized from polypeptide precursors. Together with the sympathetic nervous system and other hormones they play key roles, like an endogenous system in the regulation of the body fluid homeostasis and blood pressure. Changes in this balance lead to dysfunction in the endothel and left ventricle, which can cause severe complications. In many cardiovascular diseases natriuretic peptides serve not only as marker for diagnosis and prognosis but they have therapeutic importance. In the last years the potential use of the elevated BNP levels for diagnosis of pre-eclampsia was examined. In our review we discuss the current understanding of molecular biology, biochemistry and clinical relevance of natriuretic peptides.

Topics: Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Cardiovascular Diseases; Female; Humans; Liver Cirrhosis; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides; Pre-Eclampsia; Pregnancy; Renal Insufficiency; Shock, Septic; Tissue Distribution

Cardiac natriuretic peptides consist of a family of six peptide hormones that are synthesised by three separate genes and then stored as three separate prohormones (i.e. 126 amino acid atrial natriuretic peptide (ANP), 108 amino acid B-type natriuretic peptide (BNP) and 103 amino acid C-type natriuretic peptide (CNP) prohormones). The ANP prohormone contains four peptide hormones: long-acting natriuretic peptide (LANP), vessel dilator, kaliuretic peptide and ANP. 2. Currently, the only natriuretic peptide available commercially to treat congestive heart failure (CHF) is BNP (Nesiritide/Natrecor; SCIOS, Sunnyvale, CA, USA), which causes a small increase in the urine volume of 90 38 mL/h compared with 67 27 mL/h and no significant natriuresis, but has beneficial haemodynamic effects in acute CHF individuals. These haemodynamic effects probably contribute to the side-effects of BNP in patients with acute CHF with a 27% incidence of hypotension and possibly to 22% worsening of renal function, defined as an increase in serum creatinine of 0.5 mg/dL, associated with a worse prognosis. A review of clinical trials suggests a twofold increased risk of death at 30 days post-nesiritide treatment, a finding that needs further investigation. 3. The best of the natriuretic peptides for treating chronic CHF is the vessel dilator, which increases urinary flow up to 13-fold and sodium excretion up to fourfold, without the previously mentioned side-effects. The natriuretic and diuretic effects of vessel dilators last 6 h, which would allow them to be used on a four times per day basis in treating chronic CHF. 4. Atrial natriuretic peptide does not cause significant improvement in acute renal failure (ARF) in humans. The only natriuretic peptide that significantly improves ARF is the vessel dilator. Even when ARF has been established for 2 days before treatment in an ischaemic ARF animal model, vessel dilator decreases serum creatinine from 8.2 0.5 to 0.98 0.12 mg/dL in 6 days. At day 6 of ARF, mortality decreases to 14% (from 88%) without the vessel dilator. After 6 days of treatment with the vessel dilator, the proximal and distal tubules regenerate. 5. In cancer, vessel dilator, LANP, kaliuretic peptide and ANP at 1 mmol/L, decrease up to 97% of human breast, pancreatic and prostate adenocarcinoma cells, as well as small cell and squamous cell lung cancer cells within 24 h. In vivo, vessel dilator, LANP and kaliuretic peptide completely stop the growth of human pancreati

Topics: Animals; Atrial Natriuretic Factor; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Neoplasms; Renal Insufficiency

The fact that the heart is able to secrete hormones, which are released in significant amounts in advance of certain cardiac conditions, has resulted in a wide range of opportunities and raised a multitude of questions. These hormones, named natriuretic peptides, possess diuretic, natriuretic and vasodilatory properties. The ones used in daily clinical practice are atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and their N-terminal fragments NT-proANP and NT-proBNP, respectively. Although most studies currently involve the use of BNP, the number involving NT-proBNP is expected to increase substantially in coming years because its level is less variable and its half-life longer. Nevertheless, at present there appears to be sufficient evidence to suggest that the plasma levels of these hormones will be extremely useful for the diagnosis, prognosis, screening, pharmacological monitoring, and treatment of patients with heart failure.

Topics: Atrial Natriuretic Factor; Biomarkers; Death, Sudden, Cardiac; Heart Failure; Hospitalization; Humans; Lung Diseases; Myocardium; Natriuretic Agents; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides; Obesity; Prognosis; Renal Insufficiency; Ventricular Dysfunction, Left

Biochemical markers are available to detect cardiac involvement in many pediatric disease states and should be considered.. Analyses of three markers are readily available in clinical laboratories for improved diagnosis.. Increased workload of the heart has been associated with the release of biochemical markers (natriuretic peptides and cardiac enzymes) that indicate that a new genetic program has been activated and maladaptation is occurring in the atria, ventricles, or both. This review summarizes those that have been identified in fetal and pediatric practice. The expression of such markers is traced from early embryonic development to fetal life, to the neonate, to childhood, and then to adult life.

Topics: Adolescent; Adult; Atrial Natriuretic Factor; Biomarkers; Child; Graft Rejection; Heart Diseases; Humans; Infant; Infant, Newborn; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Renal Insufficiency; Sepsis; Troponin T

Topics: Atrial Natriuretic Factor; Biomarkers; Glomerular Filtration Rate; Humans; Natriuretic Peptide, Brain; Prognosis; Randomized Controlled Trials as Topic; Renal Dialysis; Renal Insufficiency

There is now substantial evidence supporting a role of the natriuretic peptides as a major defence mechanism against excess salt and water retention and high blood pressure. Because of this there has been considerable interest in the therapeutic potential of the natriuretic peptide system. Several approaches have been explored including the use of native peptides, the development of natriuretic peptides mimetics and targetting of endogenous clearance of natriuretic peptides. While ANP and BNP administration may be valuable in some circumstances, however, the limitations of the use of peptides especially for long-term treatment are well apparent. In view of this, considerable effort has been devoted to the development of orally active agents to enhance endogenous natriuretic peptides through inhibition of breakdown by neutral endopeptidase. This research has now led to the vasopeptidase inhibitors - dual inhibitors of both endopeptidase and angiotensin converting enzyme. These agents clearly provide a novel approach to enhance endogenous natriuretic peptide function on a background of reduced angiotensin II activity and may lead to an important advance in the treatment of hypertension and of conditions associated with overt salt and water overload.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Atrial Natriuretic Factor; Cardiovascular Diseases; Humans; Protease Inhibitors; Renal Insufficiency; Vasodilator Agents

Renal dysfunction (RD) is associated with poor outcome in systolic heart failure (HF). Left ventricular ejection fraction (LVEF) is not depressed to a greater extent in patients with RD compared to patients with normal renal function, but it is relatively unknown whether other measures of myocardial function are impaired by RD. The objective of the present study is to evaluate whether RD in systolic HF is associated with excessive impairment of myocardial function, evaluated by strain analysis and cardiac biomarkers.. Patients with LVEF <0.45% were enrolled from an outpatient HF clinic. The patients underwent advanced echocardiography. Glomerular filtration rate was estimated by the CKD-EPI equation (eGFR) and patients grouped by eGFR: eGFR group-I, ≥ 90 ml/min/1.73 m(2); eGFR group-II, 60-89 ml/min/1.73 m(2); and eGFR group-III, ≤ 59 ml/min/1.73 m(2). Multivariate regression models were developed to evaluate the associations between eGFR groups, echocardiographic measures and cardiac biomarkers.. A total of 149 patients participated in the study. Median age was 69 years, 26% were female; LVEF was 33%. Patients with a low eGFR were older (P < 0.001), but there were no differences in frequency of atrial fibrillation, hypertension, diabetes and ischemic heart disease between eGFR groups (P > 0.05 for all). RD was associated with impaired global longitudinal strain (P = 0.018), increased E/e' (P = 0.032), larger left atria (P = 0.038) and increased levels of proANP (P < 0.001), NT-proBNP (P < 0.001) and troponin I (P = 0.019) after adjustment for traditional confounders.. Echocardiographic measures and biomarkers reflecting different aspects of myocardial function are impaired in systolic HF patients with RD and the increased mortality risk in these patients may partly be explained by a depressed cardiac function.

Topics: Aged; Ambulatory Care; Atrial Natriuretic Factor; Biomarkers; Echocardiography; Female; Glomerular Filtration Rate; Heart Failure, Systolic; Humans; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Renal Insufficiency; Troponin I

Treatment with albumin in patients with cirrhosis and spontaneous bacterial peritonitis (SBP) prevents renal failure and improves survival. Whether albumin has similar beneficial effects in patients with infections other than SBP is unknown.. One hundred and ten patients with cirrhosis hospitalized for infections other than SBP were randomly assigned to receive antibiotics plus albumin (1.5 g/kgbw at diagnosis and 1 g/kgbw at day 3) (albumin group; n=56) or antibiotics alone (control group; n=54). The primary end point was survival at 3 months. Secondary end points were effects on renal and circulatory function.. The renal function, as evaluated by differences in changes in serum creatinine and estimated glomerular filtration rate between the two groups, improved in patients treated with albumin. The circulatory function improved significantly in patients treated with albumin, but not in those from the control group. There was a trend for a lower frequency of type 1 hepatorenal syndrome in the albumin group compared to the control group (1 vs. 4 patients, respectively; p=n.s.). Probability of survival at 3 months was not significantly different among the two groups. However, when adjusted for factors with independent prognostic value, treatment with albumin was an independent predictive factor of survival.. As compared with standard antibiotic therapy alone, treatment with albumin together with antibiotics has beneficial effects on the renal and circulatory function and shows a potential survival benefit. Further studies with large sample sizes should be performed to confirm these findings.

Topics: Adult; Aged; Albumins; Aldosterone; Anti-Bacterial Agents; Atrial Natriuretic Factor; Bacterial Infections; Creatinine; Drug Therapy, Combination; Female; Glomerular Filtration Rate; Hemodynamics; Humans; Kaplan-Meier Estimate; Kidney Function Tests; Liver Cirrhosis; Male; Middle Aged; Norepinephrine; Proportional Hazards Models; Renal Insufficiency; Renin; Survival Rate

This study was designed to examine the protective effects of atrial natriuretic peptide (ANP) on contrast-induced nephropathy (CIN) after coronary angiography.. Contrast-induced nephropathy is a common complication after angiography. Some studies have shown that ANP has renal protective effects, but the beneficial effects for CIN prevention remain to be clearly shown.. In a prospective, controlled, randomized trial in 254 consecutive patients with serum creatinine concentrations of > or =1.3 mg/dl, patients received either ANP (0.042 microg/kg/min; ANP group, n = 126) or Ringer solution alone (control group, n = 128). Treatment of either type was initiated 4 to 6 h before angiography and continued for 48 h.. There were no significant differences in age, sex, diabetes mellitus, or baseline serum creatinine level between the 2 groups. The prevalence of CIN, defined as a 25% increase in creatinine or an increase in creatinine of > or =0.5 mg/dl from baseline within 48 h, was significantly lower in the ANP group than in the control group (3.2% vs. 11.7%, respectively; p = 0.015). Multivariate analysis revealed that the use of >155 ml of contrast medium (odds ratio: 6.89; p < 0.001) and ANP treatment (odds ratio: 0.24; p = 0.016) were significant predictors of developing CIN. The incidence of an increase in creatinine of > or =25% or of > or =0.5 mg/dl from baseline at 1 month was also significantly lower in the ANP group than in the control group (p = 0.006).. In addition to hydration, ANP administration is effective in the prevention of CIN in patients with chronic renal failure, and the effect was maintained for 1 month.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Contrast Media; Coronary Angiography; Creatinine; Female; Humans; Iopamidol; Kidney Function Tests; Male; Multivariate Analysis; Prospective Studies; Renal Insufficiency

The purpose of this study was to determine the effect of human atrial natriuretic peptide (hANP) in patients who underwent coronary artery bypass grafting (CABG) on renal function.. Acute renal failure after cardiac surgery is associated with high morbidity and mortality.. A total of 504 patients who underwent CABG were divided into 2 groups: 1 group received hANP at 0.02 microg/kg/min from the start of cardiopulmonary bypass (hANP group), and 1 group did not receive hANP (placebo group). Various parameters were measured before and after surgery.. There was no difference in mortality between the 2 groups, but post-operative complications were less frequent in the hANP group (p = 0.0208). In the hANP group, serum creatinine (Cr) was significantly lower and urinary Cr and Cr clearance were significantly higher from post-operative day 1 to week 1. The maximum post-operative Cr level and percent increase of Cr were significantly lower in the hANP group (p < 0.0001). Patients with Cr exceeding 2.0 mg/dl included 1 in the hANP group and 8 in the placebo group, showing a significant difference (p = 0.0374). Four patients in the placebo group and none in the hANP group required hemodialysis, but the difference was not statistically significant.. Continuous infusion of low-dose hANP from the start of cardiopulmonary bypass effectively maintained post-operative renal function. Infusion of hANP prevents early post-operative acute renal failure and helps to achieve safer cardiac surgery. (. UMIN000001440).

Topics: Aged; Atrial Natriuretic Factor; Cardiopulmonary Bypass; Coronary Artery Bypass; Creatinine; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Infusions, Intravenous; Intraoperative Care; Kidney; Male; Myocardial Ischemia; Postoperative Complications; Renal Insufficiency; Treatment Outcome

We examined the mechanisms of renal resistance to atrial and brain natriuretic peptides (ANP and BNP) in pulmonary hypertension (PH). Compared to eight controls, nine PH patients showed a reduced ability to excrete an acute sodium load despite increased circulating ANP, BNP and cyclic guanosine monophosphate (cGMP), their second messenger. Patients' reduced urinary cGMP/BNP and natriuresis/urinary cGMP ratios demonstrated impaired generation of and reduced renal response to cGMP, respectively. Therefore, PH patients hyporesponsiveness to cardiac natriuretic peptides is likely located both upstream and downstream cGMP generation. Natriuretic peptide signalling pathway disruptions might be accessible to therapy.

Topics: Adult; Atrial Natriuretic Factor; Creatinine; Cyclic GMP; Down-Regulation; Female; Humans; Hypertension, Pulmonary; Kidney; Male; Middle Aged; Natriuresis; Natriuretic Peptide, Brain; Reference Values; Renal Insufficiency; Renin; Signal Transduction; Sodium Chloride

Many therapeutic measures have been employed to prevent or at least ameliorate postoperative renal impairment following liver transplantation. Recent clinical phase II studies have demonstrated that the new natriuretic peptide urodilatin has beneficial effects on renal function following heart and liver transplantation. The present study reports the first prospective randomized placebo-controlled trial of prophylactic urodilatin administration following liver transplantation. Seventy consecutive recipients of primary liver transplants were included in the study following randomization, and 33 patients continuously received urodilatin at a dose of 20 ng/kg/min for 7 d. The remaining 37 patients received a placebo infusion for the same time period. The course of serum creatinine and urea did not differ between the two groups nor did the daily urine production. However, the urodilatin group showed a higher preoperative median serum creatinine and a significant reduction on days 1 and 2, whereas this observation was not made in the placebo group. Furthermore, less furosemide was administered to the patients in the urodilatin group during the first 2 d. The incidence of postoperative hemodialysis and the number of treatments did not differ between the groups either (urodilatin group 4, vs. placebo group 6 and 22 for both groups, respectively). Side effects of the urodilatin therapy were not detected. The prophylactic low-dose urodilatin administration resulted in a trend towards amelioration of the renal function, but did not result in significant differences between the two experimental groups. Further studies, using higher doses, will be required to define the value of urodilatin for prevention of renal impairment after liver transplantation.

Topics: Adolescent; Adult; Atrial Natriuretic Factor; Creatinine; Diuretics; Drug Administration Schedule; Female; Graft Survival; Humans; Immunosuppression Therapy; Liver Transplantation; Male; Middle Aged; Peptide Fragments; Renal Dialysis; Renal Insufficiency; Statistics, Nonparametric; Survival Analysis

Salt-sensitive (SS) hypertension is accompanied with severe cardiorenal complications. In this condition, elevated blood pressure (BP) resulting from salt retention is associated with counterintuitively lower levels of atrial natriuretic peptide (ANP). In plasma, ANP is degraded by the neprilysin; therefore, pharmacological inhibition of this metalloprotease (i.e., with sacubitril) can be employed to increase ANP level. We have shown earlier that sacubitril in combination with valsartan (75 μg/day each) had beneficial effects on renal function in Dahl SS rats. The goal of this study was to evaluate the effects of a higher dose of sacubitril on renal damage in this model. To induce hypertension, male Dahl SS rats were fed a 4% NaCl diet (HS) for 21 days, and were administered sacubitril (125 μg/day) or vehicle

Topics: Aminobutyrates; Animals; Atrial Natriuretic Factor; Biphenyl Compounds; Disease Models, Animal; Dose-Response Relationship, Drug; Humans; Hypertension; Kidney Glomerulus; Male; Neprilysin; Rats; Rats, Inbred Dahl; Renal Insufficiency

Few studies have attempted to evaluate the relationship between peritoneal permeability and fluid status in peritoneal dialysis (PD). The aim of the present study was to clarify the relationship between change in the dialysate-to-plasma ratio of creatinine (D/P Cr) and change in fluid status as evaluated by natriuretic peptides. We studied 49 PD patients (29 men, 62 ± 11 years, 36.7% with diabetes) who underwent a peritoneal equilibration test at least twice after PD initiation. We evaluated correlations between the rate of change in the D/P Cr (R C-D/P Cr), the rate of change in a human atrial natriuretic polypeptide (RC-αhANP), and the rate of change in brain natriuretic peptide (RC-BNP). The RC-αhANP was strongly correlated with RC-BNP (r = 0.637, p < 0.001). In contrast, the RC-D/P Cr was not correlated with RC-αhANP (r = 0.041, p = 0.781) or with RC-BNP (r = 0.114, p = 0.435). However, positive correlations between RC-D/P Cr and RC-αhANP (r = 0.530, p = 0.006) and between RC-D/P Cr and RC-BNP (r = 0.625, p = 0.001) were observed in patients with increased D/P Cr The present study showed a positive correlation between change in peritoneal transport characteristics and change influid status in patients whose D/P Cr increased.

Topics: Aged; Atrial Natriuretic Factor; Biological Transport; Creatinine; Dialysis Solutions; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peritoneal Dialysis; Peritoneum; Permeability; Renal Insufficiency; Retrospective Studies

Renal injury is an important factor for worsening outcome in acute decompensated heart failure (ADHF). An 81-year-old woman was admitted due to ADHF with dyspnea and mild peripheral edema. The patient was managed with intravenous administration of atrial natriuretic peptide (ANP) at a dose of 0.0125 μg/kg/minute, which did not control volume overload even at an increased dose of 0.025 μg/kg/minute. After a low dose of dopamine (DA) of 1.0 μg/kg/ minute was added, urine output increased markedly to 120 from 30 mL/hour. Furthermore, her heart rate decreased to 80-100 from 120 bpm and the congestion improved with a reduced brain natriuretic peptide level. Interestingly, the combination of ANP and DA therapy reduced serum creatinine as well as the levels of urinary liver-type fatty acid binding protein, a novel reno-tubular stress marker, by 98.9%, and an oxidative stress marker, urinary 8-hydroxydeoxyguanosine, by 88.2% from baseline levels. Thus, this ADHF patient, a nonresponder to ANP alone, improved without renal injury when administered combination therapy consisting of low doses of ANP and DA, suggesting that this combined therapy might be useful for better management of ADHF in patients without diuretic responses with ANP alone. Further prospective studies are warranted.

Topics: Acute Disease; Aged, 80 and over; Atrial Natriuretic Factor; Cardiotonic Agents; Diuresis; Dopamine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Glomerular Filtration Rate; Heart Failure; Humans; Renal Insufficiency

The role of biomarkers is rapidly emerging as an important tool in the management of the cardiorenal syndromes (CRS). Natriuretic peptides (NPs), due to their low cost and rapid and accurate ability to provide additional information not surmised from clinical evaluation, are the standard bearer for the newer biomarkers. Although the NP-guided therapy has been shown to improve patient outcomes, this has yet to be demonstrated for the novel renal biomarkers. Most of the renal biomarkers studies in CRS have been performed in the setting of cardiac surgery. It will be critical to validate these new biomarkers in multicenter and prospective studies encompassing a broad spectrum of patients. Work with NPs has also shown that novel biomakers are not to be used as 'stand-alone' tests; rather they are best used as adjuncts to everything else the health care provider brings to the table. It is likely that panels of multiple biomarkers will be needed for optimal evaluation, risk stratification, timely treatment initiation and follow-up of patients with CRS.

Topics: Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Gelatinases; Glomerular Filtration Rate; Heart Failure; Humans; Hypertension; Lipocalins; Natriuretic Peptides; Neutrophils; Prognosis; Renal Insufficiency; Syndrome

Topics: Atrial Natriuretic Factor; Biomarkers; Heart Failure; Humans; Hypertension; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Renal Insufficiency

Topics: Atrial Natriuretic Factor; Contrast Media; Humans; Renal Insufficiency

Topics: Atrial Natriuretic Factor; Contrast Media; Glomerular Filtration Rate; Humans; Renal Insufficiency

Cardiovascular complications are a major problem in chronic renal failure. We examined the effects of plasma calcium, phosphate, parathyroid hormone (PTH), and calcitriol on cardiac morphology in 5/6 nephrectomized rats. Fifteen weeks after nephrectomy rats were given a control diet, high-calcium or -phosphorus diet, or given paricalcitol treatment for 12 weeks. Sham-operated rats were on a control diet. Blood pressure, plasma phosphate, and PTH were increased, while the creatinine clearance was reduced in remnant kidney rats. Phosphate and PTH were further elevated by the high-phosphate diet but suppressed by the high-calcium diet, while paricalcitol reduced PTH without influencing phosphate or calcium. The high-calcium diet increased, while the high-phosphate diet reduced plasma calcium. Plasma calcitriol was significantly reduced in other remnant kidney groups, but further decreased after paricalcitol. Cardiac perivascular fibrosis and connective tissue growth factor were significantly increased in the remnant kidney groups, and further increased in paricalcitol-treated rats. Hence, regardless of the calcium, phosphate, or PTH levels, cardiac perivascular fibrosis and connective tissue growth factor increase in rats with renal insufficiency in association with low calcitriol. Possible explanations are that aggravated perivascular fibrosis after paricalcitol in renal insufficiency may be due to further suppression of calcitriol, or to a direct effect of the vitamin D analog.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Calcitriol; Calcium; Cardiovascular System; Chronic Disease; Creatinine; Ergocalciferols; Fibrosis; Male; Nephrectomy; Parathyroid Hormone; Peptidyl-Dipeptidase A; Phosphorus; Rats; Rats, Sprague-Dawley; Renal Insufficiency; Renin

It is not known whether angiotensin II type 1 receptor antagonists can influence the function and morphology of small arteries in renal failure. We investigated the effect of 8-week losartan therapy (20 mg/kg per day) on isolated mesenteric resistance arteries by wire and pressure myographs in 5/6 nephrectomized rats. Plasma urea nitrogen was elevated 1.6-fold after nephrectomy, and ventricular synthesis of atrial and B-type natriuretic peptides was increased 2.2-fold and 1.7-fold, respectively, whereas blood pressure was not affected. Losartan did not influence these variables. The endothelium-mediated relaxation to acetylcholine was impaired in nephrectomized rats in the absence and presence of nitric oxide synthase and cyclooxygenase inhibition. Blockade of calcium-activated potassium channels by charybdotoxin and apamin reduced the remaining acetylcholine response, and this effect was less marked in nephrectomized than in sham-operated rats. Relaxation to levcromakalim, a vasodilator acting through adenosine triphosphate-sensitive potassium channels, was also impaired after nephrectomy. The arteries of nephrectomized rats showed eutrophic inward remodeling: Wall-to-lumen ratio was increased without change in wall cross-sectional area. All changes in arterial relaxation and morphology were normalized by losartan therapy. Aortic ACE content, measured by autoradiography, directly correlated to the plasma level of urea nitrogen, suggesting that renal failure has an enhancing influence on the vascular renin-angiotensin system. Losartan normalized relaxation and morphology of resistance arteries in experimental renal failure, independent of its influence on blood pressure, impaired kidney function, or volume overload. The mechanism of improved vasodilation by losartan may include enhanced relaxation through potassium channels.

Topics: Angiotensin Receptor Antagonists; Animals; Aorta; Atrial Natriuretic Factor; Blood Pressure; Endothelium, Vascular; Heart Ventricles; In Vitro Techniques; Losartan; Male; Mesenteric Arteries; Natriuretic Peptide, Brain; Nephrectomy; Peptidyl-Dipeptidase A; Potassium Channel Blockers; Potassium Channels, Calcium-Activated; Protein Precursors; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1; Renal Insufficiency; RNA, Messenger; Vasoconstriction; Vasodilation

Midwall fractional shortening (MFS) is a useful index to evaluate left ventricular myocardial function in patients with essential hypertension. The study investigated the prevalence and characterization of low MFS in hemodialysis patients.. MFS was calculated from M-mode echocardiograms in 67 patients (34 males, 33 females) receiving maintenance hemodialysis in whom fractional shortening was normal. Plasma levels of atrial and brain natriuretic peptides were also measured in these patients before and after hemodialysis. MFS was evaluated by stress-corrected MFS (ratio of observed to predicted MFS). The relationship of MFS to circumferential end-systolic stress in 122 healthy subjects was used to calculate the predicted MFS.. Stress-corrected MFS was depressed in 18 of the 67 patients (26.9%). In the low MFS group, duration of hypertension was significantly longer (p < 0.05), wall thickness was significantly greater (p < 0.001), left ventricular dimension was significantly smaller (p < 0.0001), and relative wall thickness was significantly greater (p < 0.0001) than in the normal MFS group. Reduction of brain natriuretic peptide level by hemodialysis in the low MFS group was significantly higher (p < 0.05) than in the normal MFS group.. Depression of stress-corrected MFS may be common in hemodialysis patients. Long duration of hypertension and concentric geometry of the left ventricle occur in patients with low MFS.

Topics: Aged; Atrial Natriuretic Factor; Female; Heart Ventricles; Humans; Hypertension; Male; Middle Aged; Myocardial Contraction; Natriuretic Peptide, Brain; Renal Dialysis; Renal Insufficiency; Ventricular Function, Left

Topics: Atrial Natriuretic Factor; Biomarkers; Creatinine; Cystatin C; Cystatins; Glomerular Filtration Rate; Heart Failure; Humans; Myocardial Infarction; Prognosis; Protein Precursors; Renal Insufficiency

Elderly patients with hyperkalaemia often have low concentrations of plasma renin and aldosterone, perhaps secondary to reduced glomerular filtration and sympathetic insufficiency. The endocrine response to surgical stress and volume expansion during anaesthesia was studied in seven elderly patients with hyperkalaemia (mean age 87.7 +/- SD 5.3 years), 18 elderly patients without hyperkalaemia (86.5 +/- 5.5 years), and 18 younger patients (52.6 +/- 7.2 years) as controls. Base-line values, in hyperkalaemic elderly patients, for plasma renin activity and plasma aldosterone concentration were 0.8 +/- 0.3 ng mL-1 h-1 and 2.8 +/- 0.8 pg mL-1 respectively (significantly lower than in the younger patients), and 287 +/- 42 pg mL-1 for plasma atrial natriuretic peptide levels, which were significantly higher. The plasma renin activity and aldosterone concentrations in elderly patients with hyperkalaemia were at all times lower, but not significantly, than those of the elderly patients without hyperkalaemia. The atrial natriuretic peptide concentrations (351 +/- 48 pg mL-1) in the hyperkalaemic elderly were significantly higher 90 min after induction of anaesthesia than in the normokalaemic elderly (108 +/- 38 pg mL-1). Hormone concentrations in the hyperkalaemic patients did not change during anaesthesia, but plasma atrial natriuretic peptide concentrations increased significantly in the normokalaemic elderly, and plasma renin activity and aldosterone of the younger patients increased significantly during anaesthesia. These results indicate that plasma renin activity, and the concentrations of aldosterone and of atrial natriuretic peptide in elderly patients with hyperkalaemia are unresponsive to surgical stress and volume expansion.

Topics: Adult; Aged; Aged, 80 and over; Aging; Aldosterone; Anesthesia, General; Anesthetics, Inhalation; Anesthetics, Intravenous; Atrial Natriuretic Factor; Femoral Neck Fractures; Follow-Up Studies; Glomerular Filtration Rate; Humans; Hyperkalemia; Isoflurane; Middle Aged; Nitrous Oxide; Plasma Substitutes; Potassium; Renal Insufficiency; Renin; Sodium; Stress, Physiological; Thiopental

The present investigation was designed to determine if atrial natriuretic peptides (ANPs) are increased in a spontaneous model of non-obese type 2 diabetes, the Goto-Kakizaki (GK) rat. Four peptide hormones originating from the ANP prohormone were increased twofold (P < .05) to sixfold (P < .01) in the circulation of GK rats compared with nondiabetic Wistar rats from which the GK colony was originally derived. Thus, ANP, long-acting natriuretic peptide (LANP), vessel dilator, and kaliuretic peptide were (mean +/- SE) 497 +/- 78, 1,285 +/- 105, 457 +/- 45, and 385 +/- 87 pg/mL in GK rats, versus 78 +/- 23, 542 +/- 77, 137 +/- 26, and 134 +/- 33 pg/mL, respectively, in Wistar rats. In evaluating the cause of the increased ANPs, the blood volume of GK rats (16.2 +/- 0.4 mL) was significantly (P < .01) increased compared with Wistar rats (9.5 +/- 0.3 mL). The ventricles of GK rats were not dilated when examined by transthoracic echocardiography, but the venous system was markedly distended. GK rats had a 48% to 79% decrease in renal function (ie, increased serum creatinine and blood urea nitrogen [BUN]) compared with Wistar rats. These results indicate that circulating ANPs are increased in the GK spontaneously diabetic rat secondary to (1) increased blood volume, which leads to increased synthesis and release of ANPs, and (2) renal failure, which results in a delayed metabolic processing of these peptides. The early combined increases of the four atrial peptides collectively may contribute to the hyperfiltration that occurs in early diabetes mellitus.

Topics: Animals; Atrial Natriuretic Factor; Blood Urea Nitrogen; Blood Volume; Creatinine; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Echocardiography; Hematocrit; Mice; Rats; Rats, Inbred Strains; Rats, Wistar; Renal Insufficiency; Time Factors

Radiocontrast exposure is associated with vasoconstriction of the renal vascular bed and, in certain circumstances, with acute renal failure. This may be influenced by the volume of contrast infused or underlying disease, such as diabetes or renal failure. Changes in circulating vascular regulators, such as endothelin and atrial natriuretic peptide (ANP), may play a role in the development and/or prevention of acute renal failure. Nineteen patients undergoing arteriographic procedures were divided into two groups: large-volume contrast (> or = 150 mL; n = 7) and small-volume contrast (< 150 mL; n = 12). Circulating endothelin levels increased significantly (from 12.3 +/- 1.1 pmol/L to 19.4 +/- 2.2 pmol/L; P < 0.05) following large-volume contrast exposure (group 1) but not following small-volume contrast exposure (group 2) (13.9 +/- 1.7 pmol/L to 12.2 +/- 0.09 pmol/L). ANP levels increased significantly in both groups: 43 +/- 15 pg/mL to 75 +/- 21 pg/mL in group 1 and 33 +/- 16 to 106 +/- 39 pg/mL in group 2. Data from an additional eight patients with underlying diabetes mellitus and/or renal insufficiency also were obtained and were considered separately. Endothelin levels were higher at baseline and increased significantly after contrast (25.7 +/- 5 pmol/L to 55.4 +/- 18 pmol/L) despite the relatively small average volume of contrast infused (112 +/- 15 mL). ANP levels were also highest in these patients (211 +/- 43 pg/mL precontrast and 323 +/- 65 pg/mL postcontrast). No group had a significant change in serum creatinine following contrast exposure. In conclusion, large-volume radiocontrast exposure is associated with an increase in both circulating endothelin and ANP levels. Patients with underlying diabetes or renal insufficiency may have higher baseline levels and a greater tendency to increase endothelin after contrast exposure. While an increase in endothelin may contribute to renal vasoconstriction following radiocontrast exposure, simultaneous increases in ANP may serve to offset this response and protect against changes in renal function.

Topics: Adult; Aged; Atrial Natriuretic Factor; Contrast Media; Diabetes Complications; Diabetes Mellitus; Endothelins; Female; Humans; Male; Middle Aged; Radioisotopes; Reference Values; Renal Insufficiency

This study investigated the pathogenesis of water and sodium metabolism derangements in obstructive jaundice.. Obstructive jaundice is associated with hypodipsia, depletion of extracellular water, alterations of the water and sodium regulating hormones, and an increased incidence of renal failure. Plasma atrial natriuretic factor (ANF) increases after common bile duct ligation in the rabbit. The present study was designed to investigate ANF-secreting cardiac atrial cells in this animal model.. Plasma ANF and the percentage of atrial cells staining for ANF were determined in jaundiced and sham-operated rabbits at 24 (group OJ-24, n = 11; group SO-24, n = 5) and 72 hours (group OJ-72, n = 11; group SO-72, n = 5) after surgery. The atrial ANF content was also determined.. Plasma ANF was higher in jaundiced animals than in controls both at 24 (63 +/- 44 fmol/mL vs. 17 +/- 10 fmol/mL, p < 0.02) and at 72 hours (73 +/- 49 fmol/mL vs. 12 +/- 11 fmol/mL). In the two OJ groups, the percentage of positive ANF cells per 200-power field in the right atrial appendage was higher than in the SO groups both at 24 (62 +/- 11% vs. 31 +/- 12%, p < 0.003) and at 72 hours (56 +/- 18% vs. 31 +/- 12%, p < 0.01). Similar results were obtained in the right auricular wall. The percentage of positive ANF cells was significantly higher in the left atrium in which significant differences between the OJ and SO groups were also noted. The right atrial ANF content was higher in the OJ than in SO groups (437 +/- 323 pmol/mg of protein vs. 83 +/- 44 pmol/mg of protein).. Cardiac endocrine activity is increased in experimental obstructive jaundice. ANF may be involved in the pathogenesis of the renal and water and sodium metabolic disturbances present in this disease.

Topics: Animals; Atrial Natriuretic Factor; Cholestasis; Common Bile Duct; Common Bile Duct Diseases; Heart Atria; Ligation; Rabbits; Renal Insufficiency; Water-Electrolyte Imbalance

We tested the effect of renal insufficiency, with and without angiotensin (Ang) converting enzyme (ACE) inhibition, on blood and brain atrial natriuretic factor (ANF) in rats. Two ACEs, one which penetrates into the CNS and one which does not, were used to distinguish between peripheral and central ACE effects. Rats underwent 5/6 nephrectomy (5/6-NPX) by ligation of renal arterial branches. After seven days, 28 5/6-NPX rats received lisinopril 20 mg/kg/day and 28 5/6-NPX rats received quinapril 30 mg/kg/day orally for five days, while 28 5/6-NPX control rats and 28 sham rats did not. Body weight, blood pressure, drinking and urine volume were monitored. At sacrifice, urine, plasma, and brain tissue was collected. ANF in 16 brain areas was measured by radioimmunoassay. 5/6-NPX resulted in increased blood pressure, increased urine volume, proteinuria, and increased drinking. Both ACEs lowered blood pressure to sham values and decreased proteinuria. Both ACEs increased plasma renin activity and decreased plasma ANF. However, only lisinopril decreased drinking and urine volume. 5/6-NPX increased ANF values in six brain areas, namely the periventricular preoptic nucleus, the arcuate nucleus, the perifornical nucleus, the periventricular hypothalamic nucleus, the paraventricular nucleus, and the dorsal raphe nucleus compared to sham rats. These same increases in brain ANF were also observed in 5/6-NPX rats given quinapril, compared to shams. However, lisinopril lowered ANF to sham levels in the periventricular preoptic nucleus, the arcuate nucleus, and the perifornical nucleus. In the three additional brain areas, namely the periventricular hypothalamic nucleus, the paraventricular nucleus, and the dorsal raphe nucleus, lisinopril did not effect the elevated ANF concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Atrial Natriuretic Factor; Blood-Brain Barrier; Brain; Dipeptides; Drinking; Isoquinolines; Lisinopril; Male; Nephrectomy; Quinapril; Rats; Rats, Wistar; Renal Insufficiency; Tetrahydroisoquinolines

To test the effect of converting enzyme inhibition (CEI) on diabetes, with or without renal insufficiency, we studied streptozotocin-induced diabetic rats, with or without reduced renal mass, which were treated with insulin in sufficient amounts to maintain glucose values in the mild to moderately hyperglycemic range. We found that diabetes increased glomerular filtration rate (GFR) (inulin clearance, 2.3 +/- 0.5 ml/min vs 1.9 +/- 0.1 ml/min; p < 0.05) and blood pressure (137 +/- 15 mm Hg vs 116 +/- 6 mm Hg; p < 0.05) but did not increase plasma atrial natriuretic peptide (ANP) values, when compared with control rats (72 +/- 38 vs 68 +/- 24 pg/ml). CEI decreased GFR and blood pressure to control values. In rats with diabetes and concomitantly reduced renal mass, hypertension, elevated ANP values, proteinuria, and glomerulosclerosis were prominent features. CEI was associated with reduced blood pressure (172 +/- 17 mm Hg vs 138 +/- 15 mm Hg; p < 0.05), without a concomitant decrease in GFR (1.1 +/- 0.1 ml/min vs 1.1 +/- 0.1 ml/min). Further, CEI reduced the elevated ANP values (140 +/- 34 pg/ml vs 66 +/- 19 pg/ml; p < 0.05) to those of control rats. CEI reduced proteinuria by 50% and ameliorated the histopathologic changes. In separate experiments, rats with 5/6th nephrectomy and hypertension but without diabetes were also found to have elevated ANP levels that decreased to control values with CEI. The data speak for a renal protective effect of angiotensin I-converting enzyme inhibition in this model but do not support a specific role for ANP in the model of diabetes with concomitantly reduced renal mass.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Glomerular Filtration Rate; Kidney; Male; Nephrectomy; Rats; Rats, Wistar; Renal Insufficiency