Control of renal hemodynamics during intrarenal and systemic blockade of nitric oxide synthesis in conscious dogs.

Systemic blockade of nitric oxide (NO) synthesis results in marked increases in the renal vascular resistance (RVR) and decreases in the glomerular filtration rate (GFR) and renal plasma flow (RPF). The renal hemodynamic effect of systemic NO blockade is most likely due to an integration of direct and indirect renal actions. The quantitative importance of local intrarenal blockade of NO synthesis on renal hemodynamics has not been fully elucidated. Therefore, the purpose of this study was to compare the renal hemodynamic effects of intrarenal vs. systemic NO synthesis blockade on renal hemodynamics. Nitro-L-arginine methyl ester (L-NAME) was infused intrarenally at a rate of 3 micrograms/kg/min for 180 min in conscious chronically instrumented dogs (n = 7). Intrarenal infusion of L-NAME for 180 min resulted in a 12% decrease in RPF, 14% increase in RVR, and no effect on mean arterial pressure (MAP) or GFR. In contrast, infusion of L-NAME intravenously at a rate of 10 micrograms/kg/min for 180 min increased the RVR by 124% and decreased the RPF by 55% and GFR by 45%. The MAP and heart rate both increased in response to intravenous administration of L-NAME. The results of this study suggest that the renal hemodynamic effects of systemic administration of L-NAME may, in large part, be secondary to extrarenal effects of NO synthesis blockade, possibly via activation of the sympathetic nervous system.