Effects of salt intake and angiotensin II on vascular reactivity to endothelin-1.
Hypertension produced by chronic infusion of angiotensin II (Ang II) is significantly blunted by blockade of endothelin-1 (ET-1) ET(A) subtype receptors. Furthermore, this model is salt-sensitive, and the antihypertensive response to ET(A) receptor blockade is more pronounced in animals on high salt intake. The goal of these experiments was to evaluate the effect of salt intake and Ang II on vascular reactivity to ET-1. In superior mesenteric arteries from normal male rats, studied in a standard muscle bath, incubation for 1 h with a subcontractile concentration of Ang II (10(-10) M) did not affect concentration-response curves to ET-1. Pressor responses in vivo to 2-h infusions of Ang II (5 ng/min) in rats maintained on normal or high salt intake were abolished by pretreatment with the ET(A) receptor antagonist ABT-627. The antagonist had no effect on pressor responses to phenylephrine (PE). In other experiments, rats maintained on either high or normal salt intake received continuous infusion of Ang II (5 ng/min i.v.) for 7 days, and then their superior mesenteric arteries were tested in the muscle bath. The maximum contractile response to ET-1 in arteries from Ang II-infused rats on normal salt intake was larger than in arteries from rats not receiving Ang II. Conversely, maximum responses to ET-1 in arteries from Ang II-infused rats on high salt intake were depressed compared with controls. No differences in vascular reactivity to PE were found. Thus, chronic in vivo exposure to Ang II results in specific salt-dependent changes in vascular reactivity to ET-1.
Ballew
J R
JR
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan 48824, USA.
Watts
S W
SW
Fink
G D
GD
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D012982:Sodium, Dietary / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D044022:Receptor, Endothelin A; D012982:Sodium, Dietary; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D010656:Phenylephrine