Reduced angiotensin II levels cause generalized vascular dysfunction via oxidant stress in hamster cheek pouch arterioles

Jessica R.C. Priestley, Matthew W. Buelow, Scott T. McEwen, Brian D. Weinberg, Melanie Delaney, Sarah F. Balus, Carlyn Hoeppner, Lynn Dondlinger, Julian H. Lombard

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Objectives: We investigated the effect of suppressing plasma angiotensin II (ANG II) levels on arteriolar relaxation in the hamster cheek pouch. Methods: Arteriolar diameters were measured via television microscopy during short-term (3-6. days) high salt (HS; 4% NaCl) diet and angiotensin converting enzyme (ACE) inhibition with captopril (100. mg/kg/day). Results: ACE inhibition and/or HS diet eliminated endothelium-dependent arteriolar dilation to acetylcholine, endothelium-independent dilation to the NO donor sodium nitroprusside, the prostacyclin analogs carbacyclin and iloprost, and the KATP channel opener cromakalim; and eliminated arteriolar constriction during KATP channel blockade with glibenclamide. Scavenging of superoxide radicals and low dose ANG II infusion (25ng/kg/min, subcutaneous) reduced oxidant stress and restored arteriolar dilation in arterioles of HS-fed hamsters. Vasoconstriction to topically-applied ANG II was unaffected by HS diet while arteriolar responses to elevation of superfusion solution PO2 were unaffected (5% O2, 10% O2) or reduced (21% O2) by HS diet. Conclusions: These findings indicate that sustained exposure to low levels of circulating ANG II leads to widespread dysfunction in endothelium-dependent and independent vascular relaxation mechanisms in cheek pouch arterioles by increasing vascular oxidant stress, but does not potentiate O2- or ANG II-induced constriction of arterioles in the distal microcirculation of normotensive hamsters.

Original languageEnglish (US)
Pages (from-to)134-145
Number of pages12
JournalMicrovascular Research
Volume89
DOIs
StatePublished - Sep 2013
Externally publishedYes

Bibliographical note

Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.

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