Faculty Collaboration Database

Local renal medullary L-NAME infusion enhances the effect of long-term angiotensin II treatment. Hypertension 1999 Jan;33(1 Pt 2):440-5

Date

02/04/1999

Pubmed ID

9931144

DOI

10.1161/01.hyp.33.1.440

Scopus ID

2-s2.0-17144439617 (requires institutional sign-in at Scopus site)   40 Citations

Abstract

We hypothesized that the relatively high doses of angiotensin (Ang) II required to produce hypertension in rats were related to stimulation of renal medullary nitric oxide production, which in turn blunted reductions in medullary blood flow and the development of hypertension. Ang II was infused (5 days at 3 ng. kg-1. min-1 IV) to uninephrectomized Sprague-Dawley rats in the presence and absence of a continuous medullary interstitial NG-nitro-L-arginine methyl ester (L-NAME) infusion. Renal cortical and medullary blood flows were determined with the use of implanted optical fibers and laser-Doppler flowmetry. Ang II in the absence of medullary nitric oxide synthase inhibition did not change cortical or medullary blood flow or mean arterial pressure. A threshold dose of L-NAME was determined (75 microg. kg-1. h-1) that did not produce significant short- or long-term changes in medullary blood flow and mean arterial pressure. In rats with blunted medullary nitric oxide synthase activity, Ang II infused intravenously resulted in a 30% reduction in medullary blood flow (from 1.3 to 0.9+/-0.2V) and approximately 20 mm Hg increase in mean arterial pressure with Ang II infusion over 5 days. During 70 minutes after the start of intravenous Ang II, there was an immediate reduction in medullary blood flow, with no changes in cortical blood flow or mean arterial pressure. We conclude that the relative insensitivity of rats to long-term elevations of circulating Ang II is due to the potent counterregulatory actions of the nitric oxide system, specifically within the renal medulla. The results provide novel insights of how the organism attempts to protect itself from the hypertensive effects of Ang II.

Author List

Szentiványi M Jr, Maeda CY, Cowley AW Jr

Author

Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of Wisconsin

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

Angiotensin II
Animals
Blood Pressure
Drug Synergism
Hypertension
Infusions, Intravenous
Infusions, Parenteral
Kidney Cortex
Kidney Medulla
NG-Nitroarginine Methyl Ester
Nephrectomy
Rats
Rats, Sprague-Dawley
Regional Blood Flow
Renal Circulation
Time Factors