Renal and Cardiovascular Effects of Atrial Natriuretic Peptide in Fetal Sheep

Abstract

ABSTRACT. In the adult, atrial natriuretic peptide ( A S P ) has been postulated to regulate renal and cardiovascular function both when blood volume is expanded and when atrial pressure is increased. In late gestation fetal sheep, A S P has been detected in plasma concentrations higher than in pregnant adults; however, its function in the fetus is unclear. To assess the role of A S P in mediating changes in combined ventricular output and organ blood flow, GFR, urine flow rate, and urinary sodium excretion, we studied 11 chronically cannulated fetal sheep at 126 to 131 d gestation (term 145 d). We infused A N P in doses of 27 f 4 and 55 f 8 ng/kg/min into nine of the 11 fetuses and vehicle only into the remaining two fetuses. A S P increased hematocrit, Hb, and plasma protein concentrations, which suggests that blood volume decreased. Combined ventricular output and umbilical-placental blood flow, measured by the radionuclide-labeled microsphere technique, decreased from 458 k 158 to 344 f 59 ml/min/kg and 210 f 85 to 144 f 31 ml/min/kg, respectively and the calculated umbilical-placental vascular resistance increased from 0.20 f 0.10 to 0.32 f 0.09 mm Hg/ml/min/kg during the infusion of the high A S P dose. Blood flow to the gastrointestinal tract decreased with the high dose of A N P but blood flow to all other organs, mean arterial blood pressure, and heart rate did not change significantly. The effects of A N P on fetal renal function were minimal. Thus, A S P may play a role in maintaining fluid homeostasis in the fetus through its ability to decrease blood volume and to decrease combined ventricular output and umbilicalplacental blood flow. (Pediatr Res 26: [1][2][3][4][5]1989) Abbreviations ANP, atrial natriuretic peptide i.d., inner diameter o.d., outer diameter ANP is a peptide hormone located in the cardiac atria of many adult mammalian species. Plasma concentrations of ANP increase when extracellular fluid volume is expanded or when atrial pressure is increased (1). Increased plasma concentrations of ANP have a variety of renal, cardiovascular, and endocrine effects (2). Large doses of ANP cause diuresis and natriuresis (2), a decrease in arterial blood pressure and cardiac output (3), inhibition of renin secretion after a decrease in renal perfusion pressure (4), and inhibition of aldosterone and vasopressin secre- (5,6). ANP is present in the fetal cardiac atria and ventricles (7). Basal plasma concentrations of ANP are greater in the fetus than in the pregnant adult and increase further after volume expansion and acute hypoxemia (8, 9). At present, relatively little is known about the effects of ANP in the fetus. Injection of large amounts of ANP (8 g / k g ) decreases arterial blood pressure and increases heart rate (10). However, infusion of smaller amounts of ANP (70 ng/min) increases renal excretion of sodium, potassium, and calcium, but does not change heart rate or mean arterial blood pressure (I 1). Unfortunately, the plasma concentrations at which these effects occurred were not availa...

Pulmonary Vascular Effects of Exogenous Atrial Natriuretic Peptide in Sheep Fetuses

“…Basal arterial plasma ANP concentrations are greater in the fetus than in the pregnant adult and increase further after volume expansion and acute hypoxemia (10,11). Increases in plasma ANP concentrations within a physiologic range decrease combined ventricular output and umbilical-placental blood flow (12), but do not significantly alter mean arterial blood pressure or heart rate (12,13). At present, relatively little is known about the effects of ANP on the fetal pulmonary vasculature.…”

Sympathoadrenal, Metabolic, and Regional Blood Flow Responses to Cold in Fetal Sheep

“…The technique has been reported previously (8). Blood was also collected for measurement of ANP concentrations by RIA, as described in detail previously (9). Combined ventricular output and blood flow distribution of the fetus were determined by injecting four differently labeled 15-pm microspheres (selected from 75Co, 51Cr, '"Gd, 'I4In, 54Mn, 95Nb, "'Sn, "Sr, or 65Zn; New England Nuclear, Boston, MA) into the inferior vena cava while obtaining reference samples at a rate of 4 mL/min from the descending aortic and carotid arterial catheters.…”

Fetal Endocrine Maturation and Perinatal Renal Function

“…11,84,88 Additional cardiovascular effects include decreases in fetal cardiac output andumbilical-placental blood flow. 93 Of the three natriuretic factor receptors identified, ANFR-A and ANFR-B contain guanylate cyclase catalytic domains, 94,95 and ANFR-A receptors may inhibit adenylate cyclase activity 96 The third (ANFR-C) or clearance receptor is devoid of guanylate cyclase activity and binds to an acyclic, truncated ANF analog (C-ANF). 95 ANFR-A receptors are widely distributed in adult tissues, including human placenta.…”