Inhibition of proximal tubular fluid absorption by nitric oxide and atrial natriuretic peptide in rat kidney

Abstract

Atrial natriuretic factor (ANF) and nitric oxide (NO) stimulate production of guanosine 3′,5′-cyclic monophosphate (cGMP) and are natriuretic. Split-drop micropuncture was performed on anesthetized rats to determine the effects of ANF and the NO donor sodium nitroprusside (SNP) on proximal tubular fluid absorption rate (J_va). Compared with control solutions, SNP (10⁻⁴ M) decreasedJ_va by 23% when administered luminally and by 35% when added to the peritubular perfusate. Stimulation of fluid uptake by luminal angiotensin II (ANG II; 10⁻⁹ M) was abolished by SNP (10⁻⁴ and 10⁻⁶ M). In proximal tubule suspensions, ANF (10⁻⁶ M) increased cGMP concentration to 143%, whereas SNP (10⁻⁶, 10⁻⁵, 10⁻⁴, 10⁻³ M) raised cGMP to 231, 594, 687, and 880%, respectively.S-nitroso-N-acetylpenicillamine (SNAP) also raised cGMP concentrations with similar dose-response relations. These studies demonstrate inhibition by luminal and peritubular NO of basal and ANG II-stimulated proximal fluid absorption in vivo. The ability of SNP to inhibit basal fluid uptake whereas ANF only affected ANG II-stimulated transport may be because of production of higher concentrations of cGMP by SNP.