ACE inhibition restores the vasodilator potency of the endothelium-derived relaxing factor, l- S-nitrosocysteine, in conscious Spontaneously Hypertensive rats

Stephen J. Lewis; Maleka P. Hashmi-Hill; Joy R. Owen; Kevin Sandock; Tom P. Robertson; James N. Bates

doi:10.1016/j.vph.2006.03.003

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ACE inhibition restores the vasodilator potency of the endothelium-derived relaxing factor, l- S-nitrosocysteine, in conscious Spontaneously Hypertensive rats

Journal article

Peer reviewed

ACE inhibition restores the vasodilator potency of the endothelium-derived relaxing factor, l- S-nitrosocysteine, in conscious Spontaneously Hypertensive rats

Stephen J. Lewis, Maleka P. Hashmi-Hill, Joy R. Owen, Kevin Sandock, Tom P. Robertson and James N. Bates

Vascular pharmacology, Vol.44(6), pp.491-507

06/01/2006

DOI: 10.1016/j.vph.2006.03.003

PMID: 16713366

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Abstract

The major aim of this study was to determine whether the angiotensin converting enzyme (ACE) inhibitors, captopril or enalapril, restore the diminished vasodilator potency of the endothelium-dependent agonist, acetylcholine (ACh), and the endothelium-derived relaxing factor (EDRF), l- S-nitrosocysteine (L-SNC), in conscious Spontaneously Hypertensive (SH) rats. The hemodynamic responses elicited by i.v. injections of ACh, L-SNC, and nitric oxide donors such as MAHMA NONOate, were determined in SH rats treated for 7 days with captopril, enalapril, or the direct vasodilator hydralazine. The effects of captopril, enalapril or hydralazine on oxidant stress levels in blood serum and aorta of WKY and SH rats were also determined. Captopril, enalapril and hydralazine elicited equivalent falls in mean arterial pressure and systemic vascular resistances in SH rats. ACh- and L-SNC-induced vasodilation were increased in captopril- or enalapril-treated SH rats such that the responses were equal to those in normotensive Wistar Kyoto rats. The attenuated responses of ACh and L-SNC in SH rats were not improved by hydralazine. The vasodilator effects of MAHMA NONOate, which were substantially augmented in SH rats, were not affected by captopril, enalapril or hydralazine. The levels of oxidant stress were markedly reduced in captopril- or enalapril-treated but not hydralazine-treated SH rats. The finding that the ACE inhibitors improved the vasodilator potencies of L-SNC and the EDRF released by ACh in SH rats, suggests that the diminished vasodilator potency of these compounds was due to augmented ACE activity, which increased oxidant stress levels. This study provides the first evidence to support the concept that ACE inhibition lowers arterial pressure in SH rats, at least in part, by restoring the vasodilator potency of endothelium-derived L-SNC.

Hemodynamics

Angiotensin converting enzyme

Nitric oxide

S-nitrosothiols

Spontaneously Hypertensive rats (SHR)

Details

Title: Subtitle: ACE inhibition restores the vasodilator potency of the endothelium-derived relaxing factor, l- S-nitrosocysteine, in conscious Spontaneously Hypertensive rats
Creators: Stephen J. Lewis - Case Western Reserve University
Maleka P. Hashmi-Hill - Department of Physiology and Pharmacology, University of Georgia, Athens, Georgia, USA
Joy R. Owen - Department of Physiology and Pharmacology, University of Georgia, Athens, Georgia, USA
Kevin Sandock - Department of Physiology and Pharmacology, University of Georgia, Athens, Georgia, USA
Tom P. Robertson - Department of Physiology and Pharmacology, University of Georgia, Athens, Georgia, USA
James N. Bates - University of Iowa, Anesthesia
Resource Type: Journal article
Publication Details: Vascular pharmacology, Vol.44(6), pp.491-507
Publisher: Elsevier Inc
DOI: 10.1016/j.vph.2006.03.003
PMID: 16713366
ISSN: 1537-1891
eISSN: 1879-3649
Language: English
Date published: 06/01/2006
Academic Unit: Anesthesia
Record Identifier: 9984424844002771

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