Impaired renal blood flow autoregulation in two-kidney, one-clip hypertensive rats is caused by enhanced activity of nitric oxide

Increases in renal perfusion pressure will induce shear stress-mediated nit ric oxide (NO) release, which could oppose autoregulation of renal blood fl ow (RBF). Although cardiac, cerebral, and mesenteric autoregulation is enha nced during nitric oxide (NO) synthesis inhibition, this has not been repor ted for renal autoregulation of blood flow. In the present study, the lower limit and efficiency of RBF autoregulation (as assessed by the degree of c ompensation) were studied before and during NO inhibition in normotensive S prague Dawley rats (control; n = 9) and in the non-clipped kidney of two-ki dney, one-clip Goldblatt hypertensive animals (2K1C; n = 9; 3 wk; 0.25-mm s ilver clip). In both groups, renal autoregulation curves were obtained befo re and during infusion of N-G-nitro-L-arginine (L-NNA) (bolus 1.5 mg/kg int ravenously, infusion 10 mu g/kg per min intravenously), using a transit-tim e flow probe around the left renal artery. In control rats, mean arterial p ressure (MAP) increased, RBF decreased, and renal vascular resistance (RVR) increased in response to L-NNA infusion. The lower limit of autoregulation in control animals did not significantly change during L-NNA infusion (78 +/- 3 to 70 +/- 2 mmHg). The degree of compensation in these rats slightly increased during L-NNA infusion, however, this was only significant below 9 0 mmHg. The 2K1C rats had elevated MAP under baseline conditions. L-NNA inf usion resulted in a decrease in RBF and an increase in MAP and RVR. During L-NNA infusion, RVR in 2K1C rats greatly exceeded RVR in control rats. A si gnificant decrease was observed in the lower limit of autoregulation from 8 5 +/- 3 to 72 +/- 5 mmHg (P < 0.05). In the contralateral kidney of 2K1C ra ts, the degree of compensation was lower than in control rats under baselin e conditions. L-NNA infusion resulted in significantly higher degrees of co mpensation compared to baseline. In conclusion, the contralateral kidney di splayed a high NO dependency, as RBF greatly decreased and RVR dramatically increased in response to L-NNA infusion. The contralateral kidney of 2K1C rats exhibited impaired RBF autoregulation, which was improved by NO inhibi tion, as judged from a decrease in the lower limit of autoregulation and an increase in the degree of compensation. This study indicates that perfusio n pressure-dependent NO release can oppose autoregulation in the kidney. Ho wever, the enhanced influence of NO on pressure-dependent RBF may facilitat e the preservation of renal function in the nonclipped kidney of 2K1C rats.