Oxygen consumption in the kidney: Effects of nitric oxide synthase isoforms and angiotensin II

Oxygen consumption in the kidney: Effects of nitric oxide synthase isoforms and angiotensin II.BackgroundOxygen mitochondrial effects consumption by the kidney (Qo2), is linearly related to sodium reabsorption (Tna), but recent studies suggest this relationship is variable and that metabolic efficiency (Qo2/Tna) in kidney is regulated by hormonal factors. In the dog, nonselective inhibitors of nitric oxide synthase (NOS) increase Qo2 and Qo2/Tna. Glomerular hemodynamic and reabsorptive consequences of NOS inhibition require angiotensin II (Ang II), implying an antagonistic relationship between nitric oxide and Ang II. Effects of NOS inhibition in the rat, the role of Ang II and the responsible NOS isoform have not been elucidated.MethodsKidney blood flow [renal blood flow (RBF)], glomerular filtration rate (GFR), and Qo2/Tna were measured before and during intravenous administration of NG-monomethyl-L-arginine (L-NMMA), a nonselective NOS inhibitor, in control and losartan (Ang II receptor blocker)-treated rats and rats administered S-methyl-L-thiocitrulline (SMTC), a NOS-1 inhibitor. Effects of SMTC on oxygen consumption were also examined in freshly harvested proximal tubules.ResultsL-NMMA and high-dose SMTC decreased RBF, but L-NMMA + losartan and low-dose SMTC did not. Qo2/Tna increased in both L-NMMA groups. Both low- and high-dose SMTC also increased Qo2/Tna. SMTC increased Qo2 in proximal tubules in vitro at presumed lower levels of vectorial NaCl transport. Results suggest this effect was not mediated by influences on sodium transport alone.ConclusionNonselective NOS inhibition increases the oxygen costs of kidney function independent of Ang II. Kidney NOS-1 is responsible for these in vivo and in vitro effects. In vitro observations suggest that NOS-1 acts in part via effects on basal metabolism and mitochondrial function