Angiotensin II (ANG II) receptors modulate nitric oxide (NO) effects on renal sodium (Na+) handling in conscious lambs

Abstract

ANG II and NO are considered of primary importance in maintaining Na+ homeostasis in adult mammals. Evidence suggests that NO effects on renal handling of Na+ are modulated by ANG II, yet the roles of AT1Rs and AT2Rs are not well understood. In previous studies we reported a robust natriuresis associated with the removal of endogenous NO in six week old lambs. The present experiments were designed to evaluate whether there is an interaction between AT1Rs and AT2Rs in modulating the effects of NO on tubular Na+ handling in the immature kidney. In conscious, chronically instrumented six week old lambs (N=11), renal function was measured before and after selective pharmacological inhibition of AT1Rs with ZD 7155, of AT2Rs with PD 123319, and both receptors with ZD 7155 and PD 123319, before and after removal of endogenous NO with the L‐arginine analogue, L‐NAME. The increase in fractional excretion of Na+ and Na+ clearance with L‐NAME observed previously also occurred after pretreatment with ZD 7155; this response was enhanced by combined treatment with PD 123319. Fractional Na+ reabsorption fell after ZD 7155 and L‐NAME, and decreased further after addition of PD 123319. These findings suggest that AT2Rs may potentiate the effects of AT1R on NO‐mediated Na+excretion, providing the first evidence of a cross‐talk between ATRs in modulating NO effects on Na+ homeostasis under physiologic conditions in the immature animal.