Renal responses to angiotensin II receptor blockade in ventilated preterm newborn lambs

Abstract

Renal and cardiovascular immaturity has been linked with poor outcomes in the premature human newborn. Despite extensive study in the fetus, the contribution of the renin–angiotensin system to renal and cardiovascular function in the premature newborn has not been well characterized. To evaluate the angiotensin II contribution to preterm newborn renal and cardiovascular functions, preterm (120-day) and near-term (136-day) lambs were Caesarean delivered and ventilated. One hour following delivery, animals were randomized to receive angiotensin II receptor-blockade (saralasin; 20 g kg^–1 min^–1) or saline (CON). Prior to blockade, mean SEM values for urine flow (U_Flow), urinary sodium excretion (U_NaV), and fractional excretion of sodium (FENa) were similar in all groups. Angiotensin II receptor-blockade decreased U_flow, U_NaV and FENa in the 120-day group with no changes in the 136-day animals. No changes in mean arterial pressure, or plasma angiotensin II, aldosterone, and renin activity levels were noted at either gestational age. Conclusions: (1) angiotensin II contributes to the regulation of renal function in 120-day preterm lambs without changing blood pressure and (2) angiotensin II-mediated feedback inhibition of renin release is uncoupled in preterm newborns.