LABORATORY INVESTIGATION ATRIAL NATRIURETIC PEPTIDE Effects of synthetic atrial natriuretic peptide on renal function and renin release in acute experimental heart failure

Studies were performed in anesthetized control dogs (n = 6) and in dogs (n = 6) with acute low-output heart failure produced by inflation of a balloon in the thoracic inferior vena cava. Studies were designed to determine the effects of synthetic atrial natriuretic peptide on renal function and renin release in this acute high-renin, sodium-retaining preparation. Intrarenal infusion of synthetic atrial natriuretic peptide (0.3 ,g-kgI *min1) resulted in decreases in arterial pressure and renal blood flow in both groups. Glomerular filtration rate increased in both low-output (A + 10.7 ± 3.1 ml/min) and control (A + 8.7 ± 2.9 ml/min) groups. Fractional lithium excretion, a marker of proximal tubule reabsorption, also increased in both low-output (A + 12.0 ± 4.6%) and control (A + 14.3 ± 5.0%) groups. Renin secretory rate decreased in the low-output group from 852.8 183.0 to 149.5 ± 73.7 ng/min and in the control group from 308.5 84.5 to 44.5 ± 27.5 ng/ml. Intrarenal infusion of atrial natriuretic peptide resulted in an attenuated increase in both urinary sodium excretion (A + 42.3 10.7 vs A + 201.2 ± 37.9 ,ueq/min) and fractional excretion of sodium (A + 0.48 ± 0.13% vs A + 2.85 ± 0.45%) in the low-output as compared with the control group. Our studies demonstrate that administration of synthetic atrial natriuretic peptide results in an increase in glomerular filtration rate and a decrease in proximal tubule reabsorption, as estimated by lithium excretion, in both control dogs and those with acute low-output heart failure. Furthermore, despite a decrease in arterial pressure, synthetic atrial natriuretic peptide markedly inhibits renin secretion under control conditions and in the high-renin state. Despite similar increases in glomerular filtration rate and decreases in proximal tubule reabsorption and renin release, the natriuretic response to synthetic atrial natriuretic peptide, although present, is markedly attenuated in this preparation of acute experimental heart failure. Circulation 72, No. 4, 892-897, 1985. RECENT INVESTIGATIONS have established that mammalian atria possess specific secretory granules that synthesize and release natriuretic and vasoactive peptides that have a fundamental physiologic role in regulation of cardiovascular volume. These peptides have been referred to as atrial natriuretic factor, atrial natriuretic peptides, cardionatrin, atriopeptin, and auriculin.'Previous studies from our laboratory have reported that intrarenal infusion of synthetic atrial natriuretic peptide results in a marked increase in urine volume and sodium excretion.7 This marked natriureFrom the Department of Medicine and of Physiology and Biophysics, Mayo Medical School, Rochester, MN. Supported by the American Heart Association grant-in-aid 83-964 and by the Hearst and Mayo Foundations. Terry A. Scriven was supported by an NIH Medical Student Short-Term Training grant (HL0755 1). Address for correspondence: John C. Burnett, Jr., M.D., Division of Cardiovascular Disease, Department of Medicine, Mayo Medical School, Rochester, MN 55905. Received March 15, 1985; revision accepted June 27, 1985. 892 sis is associated with a significant increase in glomerular filtration rate and a decrease in whole-kidney proximal tubule reabsorption as determined by the clearance of lithium. These studies have also demonstrated that intrarenal administration of synthetic atrial natriuretic peptide results in marked inhibition of renin release despite a sustained decrease in arterial pressure. Congestive heart failure is a syndrome characterized by sodium retention and activation of the renin-angiotensin system. To date, no studies have definitely investigated the renal hemodynamic and excretory response to atrial natriuretic peptide in a preparation of heart failure. Preliminary studies in dogs with experimental heart failure have reported that intravenous infusion of synthetic atrial natriuretic peptide is associated with a blunted natriuretic response.8 This blunted natriuretic response occurred despite an increase in creatinine clearance. Recent studies by Chimoskey et al.9 in hamsters with familial cardiomyopathy and conCIRCULATION by gest on July 6, 2017 http://ciajournals.org/ D ow nladed from LABORATORY INVESTIGATION-ATRIAL NATRIURETIC PEPTIDE gestive heart failure have shown a deficiency in atrial natriuretic peptide activity in these animals.' These investigators speculated that the abnormalities in volume regulation accompanying heart failure could in part be mediated by an absence of atrial natriuretic peptide. The present study was therefore designed to test the hypothesis that exogenous administration of atrial natriuretic peptide to dogs with acute low-output heart failure, a preparation that produces the renal and neurohumoral adjustments characteristic of congestive heart failure, would correct defects in renal sodium handling and the renin-angiotensin system. The present study investigates the effects of synthetic atrial natriuretic peptide on renal function and renin release in the presence and absence of acute low-output heart failure produced by inflation of a balloon in the thoracic inferior vena cava. Specifically, these studies focus on the effect of synthetic atrial natriuretic peptide on renal blood flow, glomerular filtration rate, proximal tubular reabsorption, renin secretion, and arterial pressure in this experimental preparation of heart failure.