Angiotensin II-1 receptors mediate both vasoconstrictor and hypertrophic responses in rat aortic smooth muscle cells.
The receptor subtypes that mediate the vasoconstrictor and hypertrophic responses of AII were evaluated in cultured aortic smooth muscle cells from rat. The AII receptors were characterized by means of the subtype-specific receptor antagonists DuP 753 (AII-1) and PD123177 (AII-2) using changes of [Ca2+]i (fura-2) as an indirect measurement of vasoconstriction and of [3H]leucine or [3H]thymidine incorporation as indices for hypertrophy and hyperplasia, respectively. AII-induced [Ca2+]i mobilization was blocked by saralasin and DuP 753 with inhibitory potency values of 2 and 1.3 x 10(-8) M, respectively, whereas PD123177 (10(-5) M) was without effect. Addition of AII (10(-7) M) to quiescent cells elicited a 45% increase in protein synthesis and a 56% increase in DNA synthesis after a 24-h exposure. These increases were blocked by both saralasin and DuP 753 (10(-5) M), but not by PD123177 (10(-5) M). Although DNA synthesis was increased by AII, no increase in smooth muscle cell number was detected. These data indicate that the AII receptors on aortic smooth muscle cells of the rat are of the AII-1 receptor subtype, which is responsible for both the vasoconstrictor and hypertrophic responses of AII.
Chiu
A T
AT
Medical Products Department, E.I. du Pont de Nemours and Company, Wilmington, DE 19880-0400.
Roscoe
W A
WA
McCall
D E
DE
Timmermans
P B
PB
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D005456:Fluorescent Dyes; D016257:Fura-2 / Q000031:analogs & derivatives; D006984:Hypertrophy / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology*; D019808:Losartan; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology*; D014661:Vasoconstriction / Q000502:physiology*
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D005456:Fluorescent Dyes; D007093:Imidazoles; D009124:Muscle Proteins; D011725:Pyridines; D011945:Receptors, Angiotensin; D013777:Tetrazoles; C049925:fura-2-am; D000804:Angiotensin II; C066253:PD 123177; D004247:DNA; D019808:Losartan; D016257:Fura-2