INHIBITION OF PROXIMAL TUBULAR FLUID ABSORPTION BY NITRIC-OXIDE AND ATRIAL-NATRIURETIC-PEPTIDE IN RAT-KIDNEY

Atrial natriuretic factor (ANF) and nitric oxide (NO) stimulate produc tion of guanosine 3',5'-cyclic monophosphate (cGMP) and are natriureti c. Split-drop micropuncture was performed on anesthetized rats to dete rmine the effects of ANF and the NO donor sodium nitroprusside (SNP) o n proximal tubular fluid absorption rate (J(va)). Compared with contro l solutions, SNP (10(-4) M) decreased J(va) by 23% when administered l uminally and by 35% when added to the peritubular perfusate. Stimulati on of fluid uptake by luminal angiotensin II (ANG II; 10(-9) M) was ab olished 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 dem onstrate inhibition by luminal and peritubular NO of basal and ANG II- stimulated proximal fluid absorption in vivo. The ability of SNP to in hibit basal fluid uptake whereas ANF only affected ANG II-stimulated t ransport may be because of production of higher concentrations of cGMP by SNP.