Faculty Collaboration Database

The vascular renin-angiotensin system contributes to blunted vasodilation induced by transient high pressure in human adipose microvessels. Am J Physiol Heart Circ Physiol 2014 Jul 01;307(1):H25-32

Date

04/30/2014

Pubmed ID

24778165

Pubmed Central ID

PMC4080172

DOI

10.1152/ajpheart.00055.2014

Scopus ID

2-s2.0-84903587126 (requires institutional sign-in at Scopus site)   19 Citations

Abstract

Increased intraluminal pressure can reduce endothelial function in resistance arterioles; however, the mechanism of this impairment is unknown. The purpose of this study was to determine the effect of local renin-angiotensin system inhibition on the pressure-induced blunting of endothelium-dependent vasodilation in human adipose arterioles. Arterioles (100-200 μm) were dissected from fresh adipose surgical specimens, cannulated onto glass micropipettes, pressurized to an intraluminal pressure of 60 mmHg, and constricted with endothelin-1. Vasodilation to ACh was assessed at 60 mmHg and again after a 30-min exposure to an intraluminal pressure of 150 mmHg. The vasodilator response to ACh was significantly reduced in vessels exposed to 150 mmHg. Exposure of the vessels to the superoxide scavenger polyethylene glycol-SOD (100 U/ml), the ANG II type 1 receptor antagonist losartan (10(-6) mol/l), or the angiotensin-converting enzyme inhibitor captopril (10(-5) mol/l) prevented the pressure-induced reduction in ACh-dependent vasodilation observed in untreated vessels. High intraluminal pressure had no effect on papaverine-induced vasodilation or ANG II sensitivity. Increased intraluminal pressure increased dihydroethidium fluorescence in cannulated vessels, which could be prevented by polyethylene glycol-SOD or losartan treatment and endothelial denudation. These data indicate that high intraluminal pressure can increase vascular superoxide and reduce nitric oxide-mediated vasodilation via activation of the vascular renin-angiotensin system. This study provides evidence showing that the local renin-angiotensin system in the human microvasculature may be pressure sensitive and contribute to endothelial dysfunction after acute bouts of hypertension.

Author List

Durand MJ, Phillips SA, Widlansky ME, Otterson MF, Gutterman DD

Authors

Matt Durand PhD Associate Professor in the Physical Medicine and Rehabilitation department at Medical College of Wisconsin
Mary F. Otterson MD Professor in the Surgery department at Medical College of Wisconsin
Michael E. Widlansky MD Associate Director, Professor in the Medicine department at Medical College of Wisconsin

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

Adipose Tissue
Arterioles
Blood Flow Velocity
Blood Pressure
Female
Humans
Male
Microcirculation
Middle Aged
Nitric Oxide
Renin-Angiotensin System
Superoxides
Vasodilation