title: Angiotensin-(1-7) and low-dose angiotensin II infusion reverse salt-induced endothelial dysfunction via different mechanisms in rat middle cerebral arteries.
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.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Durand
authors.forename: Gábor
authors.initials: G
authors.lastname: Raffai
authors.forename: Brian D
authors.initials: BD
authors.lastname: Weinberg
authors.forename: Julian H
authors.initials: JH
authors.lastname: Lombard
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000803:Angiotensin I / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002539:Cerebral Arterial Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D002536:Cerebral Arteries / Q000187:drug effects* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D007262:Infusions, Intravenous; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000009:adverse effects / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D007093:Imidazoles; D010446:Peptide Fragments; D011725:Pyridines; D017673:Sodium Chloride, Dietary; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D013481:Superoxides; D000804:Angiotensin II; C073402:PD 123319; D009599:Nitroprusside; D000803:Angiotensin I; C118790:angiotensin I (1-7); D019808:Losartan; D000109:Acetylcholine