Effects of angiotensin subtype 1 and subtype 2 receptor antagonists in normotensive versus hypertensive rats.
The purpose of this study was to examine in vivo the importance of angiotensin subtype 1 (AT1) versus subtype 2 (AT2) receptors in spontaneously hypertensive (hypertensive) versus normotensive Wistar-Kyoto (control) rats. Intravenous infusions of DuP 753, a selective AT1 receptor antagonist, abolished the pressor responses to intravenous infusions of angiotensin II in both strains, and the potency of DuP 753 in this regard was similar in the two strains. DuP 753 also abolished angiotensin II-induced aldosterone release in both strains; however, with respect to inhibiting angiotensin II-induced aldosterone release, DuP 753 was more potent in hypertensive compared with control rats. In hypertensive but not control rats, DuP 753 inhibited angiotensin II-induced aldosterone release at doses lower than required to inhibit angiotensin II-induced pressor responses. Intramesenteric infusions of DuP 753 abolished mesenteric vascular responses to intramesenteric infusions of angiotensin II with a similar potency in both strains. In control but not hypertensive rats, angiotensin II consistently potentiated noradrenergic neurotransmission in the mesenteric vascular bed, and this effect of angiotensin II was abolished by DuP 753. High doses of PD123177, a selective AT2 antagonist, did not influence any of the aforementioned effects of angiotensin II in either strain.(ABSTRACT TRUNCATED AT 250 WORDS)
Tofovic
S P
SP
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tenn.
Pong
A S
AS
Jackson
E K
EK
D000450:Aldosterone / Q000096:biosynthesis; D000803:Angiotensin I / Q000502:physiology; D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology*; D007262:Infusions, Intravenous; D019808:Losartan; D008643:Mesentery / Q000098:blood supply; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D011945:Receptors, Angiotensin / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C066253:PD 123177; D000450:Aldosterone; D000803:Angiotensin I; D019808:Losartan