Oxygen consumption in the kidney: effects of nitric oxide synthase isoforms and angiotensin II.
BACKGROUND
Oxygen mitochondrial effects consumption by the kidney (Qo(2)), is linearly related to sodium reabsorption (T(na)), but recent studies suggest this relationship is variable and that metabolic efficiency (Qo(2)/T(na)) in kidney is regulated by hormonal factors. In the dog, nonselective inhibitors of nitric oxide synthase (NOS) increase Qo(2) and Qo(2)/T(na). 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.


METHODS
Kidney blood flow [renal blood flow (RBF)], glomerular filtration rate (GFR), and Qo(2)/T(na) were measured before and during intravenous administration of N(G)-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.


RESULTS
L-NMMA and high-dose SMTC decreased RBF, but L-NMMA + losartan and low-dose SMTC did not. Qo(2)/T(na) increased in both L-NMMA groups. Both low- and high-dose SMTC also increased Qo(2)/T(na). SMTC increased Qo(2) 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.


CONCLUSIONS
Nonselective 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.
Deng
Aihua
A
Division of Nephrology-Hypertension, University of California, San Diego, California 92161, USA.
Miracle
Cynthia M
CM
Suarez
Jorge M
JM
Lortie
Mark
M
Satriano
Joseph
J
Thomson
Scott C
SC
Munger
Karen A
KA
Blantz
Roland C
RC
D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000201:enzymology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D019323:omega-N-Methylarginine / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D000804:Angiotensin II; D019323:omega-N-Methylarginine; D012964:Sodium; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D019808:Losartan