Faculty Collaboration Database

Angiotensin-(1-7) and low-dose angiotensin II infusion reverse salt-induced endothelial dysfunction via different mechanisms in rat middle cerebral arteries. Am J Physiol Heart Circ Physiol 2010 Oct;299(4):H1024-33

Date

07/27/2010

Pubmed ID

20656887

Pubmed Central ID

PMC2957344

DOI

10.1152/ajpheart.00328.2010

Scopus ID

2-s2.0-77958035132 (requires institutional sign-in at Scopus site)   47 Citations

Abstract

The goals of this study were to 1) determine the acute effect of ANG-(1-7) on vascular tone in isolated middle cerebral arteries (MCAs) from Sprague-Dawley rats fed a normal salt (NS; 0.4% NaCl) diet, 2) evaluate the ability of chronic intravenous infusion of ANG-(1-7) (4 ng·kg(-1)·min(-1)) for 3 days to restore endothelium-dependent dilation to acetylcholine (ACh) in rats fed a high-salt (HS; 4% NaCl) diet, and 3) determine whether the amelioration of endothelial dysfunction by ANG-(1-7) infusion in rats fed a HS diet is different from the protective effect of low-dose ANG II infusion in salt-fed rats. MCAs from rats fed a NS diet dilated in response to exogenous ANG-(1-7) (10(-10)-10(-5) M). Chronic ANG-(1-7) infusion significantly reduced vascular superoxide levels and restored the nitric oxide-dependent dilation to ACh (10(-10)-10(-5) M) that was lost in MCAs of rats fed a HS diet. Acute vasodilation to ANG-(1-7) and the restoration of ACh-induced dilation by chronic ANG-(1-7) infusion in rats fed a HS diet were blocked by the Mas receptor antagonist [D-ALA(7)]-ANG-(1-7) or the ANG II type 2 receptor antagonist PD-123319 and unaffected by ANG II type 1 receptor blockade with losartan. The restoration of ACh-induced dilation in MCAs of HS-fed rats by chronic intravenous infusion of ANG II (5 ng·kg(-1)·min(-1)) was blocked by losartan and unaffected by d-ALA. These findings demonstrate that circulating ANG-(1-7), working via the Mas receptor, restores endothelium-dependent vasodilation in cerebral resistance arteries of animals fed a HS diet via mechanisms distinct from those activated by low-dose ANG II infusion.

Author List

Durand MJ, Raffai G, Weinberg BD, Lombard JH

Author

Matt Durand PhD Associate Professor in the Physical Medicine and Rehabilitation department at Medical College of Wisconsin

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

Acetylcholine
Angiotensin I
Angiotensin II
Angiotensin II Type 1 Receptor Blockers
Animals
Blood Pressure
Cerebral Arterial Diseases
Cerebral Arteries
Disease Models, Animal
Dose-Response Relationship, Drug
Endothelium, Vascular
Imidazoles
Infusions, Intravenous
Losartan
Male
Nitroprusside
Peptide Fragments
Pyridines
Rats
Rats, Sprague-Dawley
Sodium Chloride, Dietary
Superoxides
Vasoconstrictor Agents
Vasodilation
Vasodilator Agents