Role of endothelin ETB receptor activation in angiotensin II-induced hypertension: effects of salt intake.
We showed recently that endothelin (ET)A receptors are involved in the salt sensitivity of ANG II-induced hypertension. The objective of this current study was to characterize the role of endothelin ETB receptor activation in the same model. Male rats on fixed normal (2 meq/day) or high (6 meq/day) salt intake received a continuous intravenous infusion of ANG II or salt only for 15 days. During the middle 5 days of the infusion period, rats were given either the selective ETB receptor antagonist A-192621 or the nonselective endothelin receptor antagonist A-182086 (both at 24 mg x kg(-1) x day(-1) intra-arterially). Infusion of ANG II caused a greater rise in arterial pressure in rats on high-salt intake. The administration of A-192621 increased arterial pressure further in all rats. The chronic hypertensive effect of A-192621 was not significantly affected by salt intake or ANG II. The administration of A-182086 lowered arterial pressure chronically only in rats on normal salt intake receiving ANG II. Thus the salt sensitivity of ANG II-induced hypertension is not caused by changes in ETB receptor function.
Ballew
J R
JR
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan 48823, USA.
Fink
G D
GD
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D065128:Endothelin Receptor Antagonists; D006977:Hypertension, Renal / Q000139:chemically induced / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008297:Male; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000378:metabolism*; D012982:Sodium, Dietary / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
C120508:A 192621; D065128:Endothelin Receptor Antagonists; D011759:Pyrrolidines; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D012982:Sodium, Dietary; D014662:Vasoconstrictor Agents; D000804:Angiotensin II