Effects of Ca2+ channel activity on renal hemodynamics during acute attenuation of NO synthesis in the rat

In cultured vascular muscle cells, nitric oxide (NO) has been shown to inhi bit voltage-dependent Ca2+ channels, which are involved in renal blood flow (RBF) autoregulation. Therefore, our purpose was to specify in vivo the ef fects of this interaction on RBF autoregulation. To do so, hemodynamics wer e investigated in anesthetized rats during Ca2+ channel blockade before or after acute NO synthesis inhibition. Rats were treated intravenously with v ehicle (n = 10), 0.3 mg/kg body wt NG-nitro-L-argininemethyl ester (L-NAME; n = 7), 4.5 mu g kg body wt(-1) min(-1) nifedipine (n = 8) alone, or with nifedipine infused before (n = 8), after (n = 8), or coadministered with L- NAME (n = 10). Baseline renal vascular resistance (RVR) averaged 14.0 +/- 1 .2 resistance units and did not change after vehicle. RVR increased or decr eased significantly by 27 and 29% after L-NAME or nifedipine, respectively. Nifedipine reversed, but did not prevent, RVR increase after or coadminist ered with L-NAME. RBF autoregulation was maintained after L-NAME, but the a utoregulatory pressure limit (P-A) was significantly lowered by 15 mmHg. Ni fedipine pretreatment or coadministration with L-NAME limited PA resetting or suppressed autoregulation at higher doses. Results were similar with ver apamil. Intrarenal blockade of Ca2+-activated Ki channels also prevented au toregulatory resetting by L-NAME (n = 8). These findings suggest NO inhibit s voltage-dependent Ca2+ channels and thereby modulates RBF autoregulatory efficiency.