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

Masao Kakoki, Ai Ping Zou, David L. Mattson

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67 Scopus citations

Abstract

The role of nitric oxide (NO) produced by NO synthase 1 (NOS1) in the renal vasculature remains undetermined. In the present study, we investigated the influence of systemic inhibition of NOS1 by intravenous administration of Nω-propyl-L-arginine (L-NPA; 1 mg·kg-1·h-1) and N5-(1-imino-3-butenyl)-L-ornithine (v-NIO; 1 mg·kg-1·h-1), highly selective NOS1 inhibitors, on renal cortical and medullary blood flow and interstitial NO concentration in Sprague-Dawley rats. Arterial blood pressure was significantly decreased by administration of both NOS1-selective inhibitors (-11 ± 1 mmHg with L-NPA and -7 ± 1 mmHg with v-NIO; n = 9/group). Laser-Doppler flowmetry experiments demonstrated that blood flow in the renal cortex and medulla was not significantly altered following administration of either NOS1-selective inhibitor. In contrast, the renal interstitial level of NO assessed by an in vivo microdialysis oxyhemoglobin-trapping technique was significantly 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 infusion of the nonspecific NOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME; 50 mg·kg-1·h-1) to rats pretreated with either of the NOS1-selective 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 (73-77%) and medulla (62-71%). To determine if a 40% decrease in NO could alter 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 interstitial NO (cortex 39%, medulla 38%) and significantly decreased blood flow (cortex 23-24%, medulla 31-33%). These results suggest that NOS1 does not regulate basal blood flow in the renal cortex or medulla, despite the observation that a considerable portion of NO in the renal interstitial space appears to be produced by NOS1.

Original languageEnglish (US)
Pages (from-to)R91-R97
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume281
Issue number1 50-1
DOIs
StatePublished - 2001

Keywords

  • Laser-Doppler flowmetry
  • Microdialysis
  • Spectrophotometry

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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