The renin-angiotensin system in conscious newborn sheep: Metabolic clearance rate and activity

Abstract

The role of the renin-angiotensin system (RAS) in regulating newborn mean arterial blood pressure (MAP) and tissue blood flow remains unclear. Although postnatal MAP increases, vascular responsiveness to infused angiotensin II (ANG II) is unchanged, possibly reflecting increased metabolic clearance rate of ANG II (MCRANG II). To address this, we examined MAP, heart rate, plasma ANG II and renin activity (PRA), and MCRANG II in conscious postnatal sheep (n = 9, 5-35 d old) before and during continuous systemic ANG II infusions to measure MCRANG II. Postnatal MAP increased (p < 0.02), whereas plasma ANG II decreased from 942 ± 230 (SEM) to 471 ± 152 and 240 ± 70 pg/mL at <10 d, 10-20 d, and 21-35 d postnatally (p = 0.05), respectively. Despite high plasma ANG II, PRA remained elevated, averaging 6.70 ± 1.1 ng/mL·h throughout the postnatal period, but decreased 35% (p = 0.01) during ANG II infusions. MCRANG II decreased approximately sixfold after birth and averaged 115 mL/min·kg during the first month. Circulating ANG II is markedly increased after birth, reflecting placental removal, high fetal MCRANG II, and enhanced RAS activity. Although circulating ANG II decreases as MAP increases, MCRANG II is unchanged, suggesting decreased ANG II production. Persistent vascular smooth muscle (VSM) AT2 receptor subtype (AT2R) expression after birth may modify the hypertensive effects of ANG II postnatally. © International Pediatrics Research Foundation, Inc. 2007. All Rights Reserved.