Tanoi C, Suzuki Y, Shibuya M, Sugita K, Masuzawa-Ito K, Asano M
Department of Neurosurgery, Nagoya University School of Medicine, Japan.
J Cardiovasc Pharmacol. 1992 Apr;19(4):568-79. doi: 10.1097/00005344-199204000-00014.
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.
比较了内皮素 -1（ET）对犬脑动脉（基底动脉、大脑后动脉和大脑中动脉）和外周动脉（冠状动脉和肠系膜动脉）去内皮条的血管收缩作用。ET在这些动脉中产生浓度依赖性收缩。ET在基底动脉、大脑后动脉、大脑中动脉和冠状动脉中的阈浓度和半数有效浓度（EC50）值显著低于肠系膜动脉。在基底动脉中，硝苯地平使ET的浓度 - 反应曲线向右移位，且对ET的最大反应显著降低。另一方面，硝苯地平在肠系膜动脉中对ET表现出典型的非竞争性拮抗作用。在细胞外钾离子浓度升高的情况下测定的肠系膜动脉对ET的收缩反应，与在正常钾离子浓度下测定的基底动脉对该肽的反应相当。当置于含0.1 mM乙二醇双四乙酸（EGTA）的无钙溶液（0 - Ca溶液）中时，脑动脉和冠状动脉从静息水平显著舒张，而肠系膜动脉未出现这种情况。向浸泡在0 - Ca溶液中的脑动脉和冠状动脉重新添加钙离子会引起双相收缩，这种收缩易被硝苯地平抑制。当在钙离子诱导的收缩之前引入浓度低于10⁻⁹ M的ET时，该肽未产生可检测到的收缩，但增强了钙离子诱导的收缩。ET诱导的增强程度在脑动脉和冠状动脉中比在肠系膜动脉中更大。即使在0 - Ca溶液中，较高浓度的ET（1×10⁻⁸和3×10⁻⁸ M）产生的收缩在基底动脉中比在肠系膜动脉中更弱。这些结果表明，与肠系膜动脉相比，脑动脉和冠状动脉对较低浓度（低于10⁻⁹ M）的ET表现出更强的收缩。脑动脉和冠状动脉对ET这些增强反应的一种可能原因似乎是，这些动脉中的电压依赖性钙离子通道在静息状态下比肠系膜动脉中的更易被激活。
