Comparison of vasoconstrictor actions of endothelin-1 in cerebral, coronary, and mesenteric arteries of the dog.
Vasoconstrictor actions of endothelin-1 (ET) were compared between endothelium-removed strips of cerebral (basilar, posterior cerebral, and middle cerebral) and peripheral (coronary and mesenteric) arteries of the dog. ET produced a concentration-dependent contraction in these arteries. A threshold concentration and EC50 value for ET were significantly lower in the basilar, posterior cerebral, middle cerebral, and coronary arteries than in the mesenteric artery. In the basilar artery, nifedipine caused a rightward displacement of the concentration-response curve for ET with a significant reduction in the maximum response to ET. On the other hand, nifedipine showed a typical noncompetitive antagonism against ET in the mesenteric artery. Contractile responses of the mesenteric artery to ET determined under an elevation of extracellular K+ concentration were comparable to the responses of the basilar artery to this peptide determined under normal K+ concentrations. The cerebral and coronary arteries, but not the mesenteric artery, relaxed significantly from the resting level when placed in a Ca(2+)-free solution containing 0.1 mM EGTA (0-Ca solution). The readdition of Ca2+ to the cerebral and coronary arteries soaked in the 0-Ca solution caused a biphasic contraction that was susceptible to inhibition by nifedipine. When ET in concentrations below 10(-9) M was introduced before the Ca(2+)-induced contraction, this peptide produced no detectable contraction, but potentiated the Ca(2+)-induced contraction. The extent of potentiation induced by ET was much greater in the cerebral and coronary arteries than in the mesenteric artery. Even in the 0-Ca solution, higher concentrations of ET (1 x 10(-8) and 3 x 10(-8) M) produced a contraction that was weaker in the basilar artery than in the mesenteric artery. These results indicate that the cerebral and coronary arteries exhibited more potent contractions in response to lower concentrations (below 10(-9) M) of ET than the mesenteric artery. A likely possibility for these enhanced responses to ET in the cerebral and coronary arteries appears to be that the voltage-dependent Ca2+ channels 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-Ito
K
K
Asano
M
M
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D016232:Endothelins; D009543:Nifedipine; D011188:Potassium; D002118:Calcium