Role of ET(A) receptors in experimental ANG II-induced hypertension in rats.
The objectives were to determine if ANG II-induced hypertension is maintained by activation of endothelin type A (ET(A)) receptors by endogenous ET-1 and if this effect is influenced by salt intake. Male rats were maintained on high sodium intake (HS; 6 meq/day) or on normal sodium intake (NS; 2 meq/day). Hypertension was produced by intravenous infusion of ANG II (5 ng/min) for 15 days. Five-day oral dosing with the selective ET(A)-receptor antagonist ABT-627 (~2 mg. kg(-1). day(-1)) reduced mean arterial pressure (MAP) to baseline levels in rats on HS receiving ANG II infusion, but it did not affect MAP in normotensive HS controls. In rats on NS, ABT-627 only transiently decreased MAP in rats receiving ANG II and slightly reduced MAP in normotensive controls. ABT-627 produced mild retention of sodium and water in NS rats receiving ANG II, but not in any other group. These results indicate that ET-1 plays a role in ANG II-induced hypertension via activation of ET(A) receptors and that this role is more prominent in rats on HS.
Ballew
J R
JR
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan 48824, USA.
Fink
G D
GD
D000804:Angiotensin II; D000818:Animals; D000077868:Atrasentan; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D065128:Endothelin Receptor Antagonists; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism*; D008297:Male; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000378:metabolism*; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D014662:Vasoconstrictor Agents; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology
D065128:Endothelin Receptor Antagonists; D011759:Pyrrolidines; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; D017673:Sodium Chloride, Dietary; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D000077868:Atrasentan