Renal cortical and medullary blood flow responses to L-NAME and ANG II in wild-type, nNOS null mutant, and eNOS null mutant mice

David L. Mattson, Carla J. Meister

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Experiments in wild-type (WT; C57BL/6J) mice, endothelial nitric oxide synthase null mutant [eNOS(-/-)] mice, and neuronal NOS null mutant [nNOS(-/-)] mice were performed to determine which NOS isoform regulates renal cortical and medullary blood flow under basal conditions and during the infusion of ANG II. Inhibition of NOS with Nω-nitro-L-arginine methyl ester (L-NAME; 50 mg/kg iv) in Inactin-anesthetized WT and nNOS(-/-) mice increased arterial blood pressure by 28-31 mmHg and significantly decreased blood flow in the renal cortex (18-24%) and the renal medulla (13-18%). In contrast, blood pressure and renal cortical and medullary blood flow were unaltered after L-NAME administration to eNOS(-/-) mice, indicating that NO derived from eNOS regulates baseline vascular resistance in mice. In subsequent experiments, intravenous ANG II (20 ng·kg-1-min-1) significantly decreased renal cortical blood flow (by 15-25%) in WT, eNOS(-/-), nNOS(-/-), and WT mice treated with L-NAME. The infusion of ANG II, however, led to a significant increase in medullary blood flow (12-15%) in WT and eNOS(-/-) mice. The increase in medullary blood flow following ANG II infusion was not observed in nNOS(-/-) mice, in WT or eNOS(-/-) mice pretreated with L-NAME, or in WT mice administered the nNOS inhibitor 5-(1-imino-3-butenyl)-L-ornithine (1 mg·kg-1·h-1). These data demonstrate that NO from eNOS regulates baseline blood flow in the mouse renal cortex and medulla, while NO produced by nNOS mediates an increase in medullary blood flow in response to ANG II.

Original languageEnglish (US)
Pages (from-to)R991-R997
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume289
Issue number4 58-4
DOIs
StatePublished - Oct 2005

Keywords

  • Angiotensin II
  • Endothelial and neuronal nitric oxide synthase
  • Kidney
  • Laser-Doppler flowmetry
  • Mice
  • N-nitro-L- arginine
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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