Endothelium-dependent contractions induced by angiotensin I and angiotensin II in canine cerebral artery.
Whether angiotensin I and angiotensin II caused endothelium-dependent contraction was examined in canine cerebral arteries. In endothelium-intact preparations, angiotensin I and angiotensin II at 10(-8) to 10(-6) M caused dose-dependent contractions, whereas both angiotensins caused much less contractions in endothelium-removed preparations. The contractions induced by angiotensin I and angiotensin II were strongly attenuated by aspirin (cyclooxygenase inhibitor) (5 x 10(-5) M), OKY-046 [thromboxane (TX) A2 synthetase inhibitor] (10(-5) M) and ONO-3708 (TX)A2 antagonist) (5 X 10(-9) M). Captopril (10(-6) M) significantly attenuated the contractions induced by angiotensin I but not those induced by angiotensin II. Angiotensin I- and angiotensin II- induced contractions were inhibited markedly by Sar1, Ala8-angiotensin II (10(-9) and 10(-8) M). The present experiments demonstrate that angiotensin I and angiotensin II produce endothelium-dependent contraction in canine cerebral artery via a factor which appears to be TXA2. Angiotensin I may be converted by endothelial cells to angiotensin II, which may activate the cells to produce TXA2 in canine cerebral artery.
Manabe
K
K
Department of Pharmacology, Faculty of Medicine, Kyoto University, Japan.
Shirahase
H
H
Usui
H
H
Kurahashi
K
K
Fujiwara
M
M
D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects*; D004285:Dogs; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D014661:Vasoconstriction / Q000187:drug effects*
D000804:Angiotensin II; D000803:Angiotensin I