Acute and chronic angiotensin-(1-7) restores vasodilation and reduces oxidative stress in mesenteric arteries of salt-fed rats. Am J Physiol Heart Circ Physiol 2011 Oct;301(4):H1341-52
Date
08/02/2011Pubmed ID
21803946Pubmed Central ID
PMC3197355DOI
10.1152/ajpheart.00202.2011Scopus ID
2-s2.0-80053276066 (requires institutional sign-in at Scopus site) 53 CitationsAbstract
This study determined the effect of ANG-(1-7) on salt-induced suppression of endothelium-dependent vasodilatation in the mesenteric arteries of male Sprague-Dawley rats. Chronic intravenous infusion of ANG-(1-7), oral administration of the nonpeptide mas receptor agonist AVE-0991, and acute preincubation of the arteries with ANG-(1-7) and AVE-0991 all restored vasodilator responses to both ACh and histamine that were absent in the arteries of rats fed a high-salt (4% NaCl) diet. The protective effects of ANG-(1-7) and AVE-0991 were inhibited by acute or chronic administration of the mas receptor antagonist A-779, the ANG II type 2 (AT(2)) receptor blocker PD-123319, or N-nitro-l-arginine methyl ester, but not the ANG II type 1 receptor antagonist losartan. Preincubation with the antioxidant tempol or the nitric oxide (NO) donor diethylenetriamine NONOate and acute and chronic administration of the AT(2) receptor agonist CGP-42112 mimicked the protective effect of ANG-(1-7) to restore vascular relaxation. Acute preincubation with ANG-(1-7) and chronic infusion of ANG-(1-7) ameliorated the elevated superoxide levels in rats fed a high-salt diet, but the expression of Cu/Zn SOD and Mn SOD enzyme proteins in the vessel wall was unaffected by ANG-(1-7) infusion. These results indicate that both acute and chronic systemic administration of ANG-(1-7) or AVE-0991 restore endothelium-dependent vascular relaxation in salt-fed Sprague-Dawley rats by reducing vascular oxidant stress and enhancing NO availability via mas and AT(2) receptors. These findings suggest a therapeutic potential for mas/AT(2) receptor activation in preventing the vascular oxidant stress and endothelial dysfunction associated with elevated dietary salt intake.
Author List
Raffai G, Durand MJ, Lombard JHAuthor
Matt Durand PhD Associate Professor in the Physical Medicine and Rehabilitation department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Angiotensin IAngiotensin II Type 1 Receptor Blockers
Animals
Blood Pressure
Blotting, Western
Ethidium
Fluorescent Dyes
Male
Mesenteric Arteries
Nitric Oxide
Oligopeptides
Oxidative Stress
Peptide Fragments
Rats
Rats, Sprague-Dawley
Sodium, Dietary
Superoxide Dismutase
Superoxides
Up-Regulation
Vasodilation
Vasodilator Agents
