Mechanism of the enhanced vasoconstrictor responses to endothelin-1 in canine cerebral arteries.
Vasoconstrictor effects of endothelin-1 (ET) were investigated in endothelium-denuded strips of cerebral (basilar and posterior cerebral) and mesenteric arteries of the dog. ET produced a concentration-dependent contraction in these arteries. Contractile responses to lower concentrations (below 3 x 10(-10) M) of ET were significantly greater in the cerebral arteries than in the mesenteric artery. Inhibition by nifedipine of the contractile responses to ET was greater in the basilar artery than in the mesenteric artery. After the inhibition by 10(-7) M in the mesenteric artery. After the inhibition by 10(-7) M nifedipine, the remaining responses to ET were similar in the two arteries. Cerebral arteries, but not the mesenteric artery, relaxed significantly from the resting level when placed in a Ca2(+)-free solution containing 0.1 mM EGTA (0-Ca solution). Readdition of Ca2+ to the cerebral arteries placed in the 0-Ca solution caused a biphasic contraction that was sensitive to nifedipine. When 10(-9) M ET was introduced before the Ca2(+)-induced contraction, this peptide produced only a very small contraction, but enhanced the Ca2(+)-induced contraction. The extent of the enhancement induced by ET was much greater in the cerebral arteries than in the mesenteric artery. These results indicate that the enhanced responses to ET in the cerebral arteries were dependent to a large extent on Ca2+ influx through voltage-dependent Ca2+ channels (VDCs). It is likely that the VDCs in these arteries are more activated in the resting state than those in the mesenteric artery.
Tanoi
C
C
Department of Neurosurgery, Nagoya University School of Medicine, Japan.
Suzuki
Y
Y
Shibuya
M
M
Sugita
K
K
Masuzawa
K
K
Asano
M
M
D000818:Animals; D001488:Basilar Artery / Q000502:physiology; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D002536:Cerebral Arteries / Q000502:physiology*; D004285:Dogs; D004533:Egtazic Acid / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D015220:Calcium Channels; D016232:Endothelins; D004533:Egtazic Acid; D009543:Nifedipine; D002118:Calcium