Effect of Acute Nitric Oxide Synthesis Inhibition on Kidney Function in Experimental Renovascular Hypertension 1796

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Nitric oxide plays an important role in regulating renal hemodynamics. We compared the responses of anesthetized two kidney, one clip renovascular hypertensive rats to acute mean arterial pressure [MAP] elevations caused by either the nitric oxide synthesis inhibitor L-NAME 8 mg/kg IV (n = 8) or by infrarenal aortic constriction [CONST] (n = 6). Results are mean ± SE and *P < 0.05 vs pretreatment measurements. Pretreatment MAP was 125± 2 mmHg, rising to 149 ± 4* mmHg after L-NAME and to 146± 2* mmHg after CONST. L-NAME reduced plasma concentrations of the nitric oxide metabolites, nitrite/nitrate (28 ± 1 vs 19 ± 3* umol/L) while CONST had no significant effect on these levels (28 ± 1 vs 29 ± 2 umol/L). In unclipped kidneys, L-NAME did not significantly alter glomerular filtration rate (1.2 ± 0.2 vs 1.0± 0.2 ml/min per g kidney wt), decreased renal plasma flow (2.6± 0.1 vs 1.6 ± 0.3* ml/min per g kidney wt), increased urine flow (12 ± 3 vs 47 ± 12* ul/min per g kidney wt), and did not significantly affect urine nitrite/nitrate excretion (2.5 ± 0.3 vs 3.0± 0.5 nmol/min per g kidney wt); while CONST did not significantly alter either glomerular filtration rate (0.9 ± 0.1 vs 0.9 ± 0.1 ml/min per g kidney wt) or renal plasma flow (2.9 ± 0.1 vs 2.8 ± 0.3 ml/min per g kidney wt) and increased both urine flow (10 ± 3 vs 39± 9* ul/min per g kidney wt) and urine nitrite/nitrate excretion (2.1± 0.2 vs 4.3 ± 0.4* nmol/min per g kidney wt). Inclipped kidneys, both L-NAME and CONST did not significantly affect glomerular filtration rate (L-NAME 0.8 ± 0.1 vs 1.0 ± 0.2 ml/min per g kidney wt; CONST 0.8 ± 0.1 vs 0.9 ± 0.1 ml/min per g kidney wt) and increased renal plasma flow (L-NAME 1.9 ± 0.3 vs 2.5± 0.3* ml/min per g kidney wt; CONST 2.2 ± 0.3 vs 2.7 ± 0.2* ml/min per g kidney wt), urine flow (L-NAME 8 ± 3 vs 38 ± 11* ul/min per g kidney wt; CONST 7 ± 3 vs 31 ± 7* ul/min per g kidney wt) and urine nitrite/nitrate excretion (L-NAME 1.8 ± 0.3 vs 3.2± 0.5* nmol/min per g kidney wt; CONST 1.4 ± 0.2 vs 2.9 ± 0.3* nmol/min per g kidney wt). Our results suggest that the influence of nitric oxide on kidney function varies with renal perfusion pressure and that plasma and urine nitrite/nitrate measurements can be used as indices of nitric oxide activity in vivo.