Asano M, Aoki K, Suzuki Y, Matsuda T
Department of Pharmacology, Nagoya City University Medical School, Japan.
J Pharmacol Exp Ther. 1987 Nov;243(2):646-56.
Vasoconstrictor effects of Bay k 8644, a dihydropyridine Ca++ agonist, and vasorelaxant effects of nifedipine were investigated in helical strips of dog cerebral (basilar, posterior cerebral and middle cerebral) and peripheral (coronary and mesenteric) arteries. The addition of Bay k 8644 produced a dose-dependent contraction in the absence of any contractile agent in the basilar artery with a pD2 value of 8.53. Similar sensitivity to Bay k 8644 was observed in the posterior cerebral, middle cerebral or coronary artery. Bay k 8644 was much less effective in producing a contraction in the mesenteric artery. An elevation of the concentration of extracellular K+ eliminated the difference between the responses to Bay k 8644 in the basilar and mesenteric artery. Contractile responses of the basilar artery to Bay k 8644 were antagonized competitively by nifedipine (pA2 = 8.17), but non-competitively by diltiazem. The pA2 values for nifedipine antagonism of Bay k 8644 responses with the elevated K+ were the same between the basilar and mesenteric arteries. Increased sensitivity to exogenously added K+ also was observed in cerebral and coronary arteries when compared with the mesenteric artery. The addition of nifedipine to an unstimulated strip produced a dose-dependent relaxation in cerebral and coronary arteries, but not in the mesenteric artery. When the cerebral and peripheral arteries were contracted with K+ to the same magnitude, nifedipine produced similar relaxations among these arteries. Nifedipine was less efficacious in antagonizing the contractile response to Bay k 8644 compared with the contractile response to K+ in cerebral arteries. These results suggest that 1) the voltage-dependent Ca++ channels in the cerebral and coronary arteries are in different states of activation from those in the mesenteric artery, 2) Bay k 8644 contracts the cerebral and coronary arteries by acting primarily on the same site, presumably dihydropyridine receptors of the voltage-dependent Ca++ channels at which nifedipine acts, 3) the dihydropyridine receptors were the same between the basilar and mesenteric arteries and 4) there may be a difference in the state of the Ca++ channel in the arteries between the stimulation with Bay k 8644 and K+-depolarization.
在犬脑动脉（基底动脉、大脑后动脉和大脑中动脉）及外周动脉（冠状动脉和肠系膜动脉）的螺旋条带上，研究了二氢吡啶类钙离子激动剂Bay k 8644的血管收缩作用以及硝苯地平的血管舒张作用。在无任何收缩剂的情况下，加入Bay k 8644可使基底动脉产生剂量依赖性收缩，其pD2值为8.53。在大脑后动脉、大脑中动脉或冠状动脉中观察到对Bay k 8644的类似敏感性。Bay k 8644在肠系膜动脉中引起收缩的效果要差得多。细胞外钾离子浓度升高消除了基底动脉和肠系膜动脉对Bay k 8644反应的差异。基底动脉对Bay k 8644的收缩反应可被硝苯地平竞争性拮抗（pA2 = 8.17），但被地尔硫䓬非竞争性拮抗。在升高钾离子的情况下，硝苯地平拮抗Bay k 8644反应的pA2值在基底动脉和肠系膜动脉之间相同。与肠系膜动脉相比，在脑动脉和冠状动脉中也观察到对外源性添加钾离子的敏感性增加。在未受刺激的条带上加入硝苯地平可使脑动脉和冠状动脉产生剂量依赖性舒张，但对肠系膜动脉无此作用。当脑动脉和外周动脉用钾离子收缩至相同程度时，硝苯地平在这些动脉中产生类似的舒张作用。与脑动脉中对钾离子的收缩反应相比，硝苯地平拮抗对Bay k 8644的收缩反应的效果较差。这些结果表明：1）脑动脉和冠状动脉中电压依赖性钙离子通道的激活状态与肠系膜动脉中的不同；2）Bay k 8644主要通过作用于同一部位（推测为硝苯地平作用的电压依赖性钙离子通道的二氢吡啶受体）使脑动脉和冠状动脉收缩；3）基底动脉和肠系膜动脉中的二氢吡啶受体相同；4）在用Bay k 8644刺激和钾离子去极化时，动脉中钙离子通道的状态可能存在差异。
