The influence of nitric oxide synthase 1 on blood flow and interstitial nitric oxide in the kidney

The role of nitric oxide (NO) produced by NO synthase 1 (NOS1) in the renal vasculature remains undetermined. In the present study, we investigated th e influence of systemic inhibition of NOS1 by intravenous administration of N-omega-propyl-L-arginine (L-NPA; 1 mg.kg(-1).h(-1)) and N-5-(1-imino-3-bu tenyl)-L-ornithine (v-NIO; 1 mg.kg(-1).h(-1)), highly selective NOS1 inhibi tors, on renal cortical and medullary blood flow and interstitial NO concen tration in Sprague-Dawley rats. Arterial blood pressure was significantly d ecreased by administration of both NOS1-selective inhibitors (-11 +/- 1 mmH g with L-NPA and -7 +/- 1 mmHg with v-NIO; n = 9/group). Laser-Doppler flow metry experiments demonstrated that blood flow in the renal cortex and medu lla was not significantly altered following administration of either NOS1-s elective inhibitor. In contrast, the renal interstitial level of NO assesse d by an in vivo microdialysis oxyhemoglobin-trapping technique was signific antly decreased in both the renal cortex (by 36-42%) and medulla (by 32-40% ) following administration of L-NPA (n = 8) or v-NIO (n = 8). Subsequent in fusion of the nonspecific NOS inhibitor N-omega-nitro-L-arginine methyl est er (L-NAME; 50 mg.kg(-1).h(-1))to rats pretreated with either of the NOS1-s elective inhibitors significantly increased mean arterial pressure by 38-45 mmHg and significantly decreased cortical (25-29%) and medullary (37-43%) blood flow. In addition, L-NAME further decreased NO in the renal cortex (7 3-77%) and medulla (62-71%). To determine if a 40% decrease in NO could alt er renal blood flow, a lower dose of L-NAME (5 mg.kg(-1).h(-1); n = 8) was administered to a separate group of rats. The low dose of L-NAME reduced in terstitial NO (cortex 39%, medulla 38%) and significantly decreased blood f low (cortex 23-24%, medulla 31-33%). These results suggest that NOS1 does n ot regulate basal blood flow in the renal cortex or medulla, despite the ob servation that a considerable portion of NO in the renal interstitial space appears to be produced by NOS1.