Medical College of Wisconsin
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Renal cortical and medullary blood flow responses to L-NAME and ANG II in wild-type, nNOS null mutant, and eNOS null mutant mice. Am J Physiol Regul Integr Comp Physiol 2005 Oct;289(4):R991-7

Date

06/18/2005

Pubmed ID

15961532

DOI

10.1152/ajpregu.00207.2005

Scopus ID

2-s2.0-25844500876 (requires institutional sign-in at Scopus site)   55 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 N(omega)-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 x kg(-1) x 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 x kg(-1) x 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.

Author List

Mattson DL, Meister CJ



MESH terms used to index this publication - Major topics in bold

Angiotensin II
Animals
Blood Flow Velocity
Kidney Cortex
Kidney Medulla
Male
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Mice, Transgenic
Mutation
NG-Nitroarginine Methyl Ester
Nerve Tissue Proteins
Nitric Oxide Synthase
Nitric Oxide Synthase Type I
Nitric Oxide Synthase Type II
Nitric Oxide Synthase Type III
Renal Circulation