Effects of calcium antagonists on vascular endothelial, smooth muscle and sympathetic nerve functions

观察钙拮抗剂对狗离体动脉条对直接血管收缩剂（前列腺素F_<2alpha>）、EDRF释放剂（P物质）和神经刺激的机械反应的影响。nicardipine （l型钙通道抑制剂）、氟桂嗪和AE0047（一种新的二氢吡啶衍生物）可抑制前列腺素F_<2alpha>引起的收缩，omega- concontoxin （n型钙通道抑制剂）不能抑制。nicardipine、omega- concontoxin和tetramethrin （t型通道抑制剂）均不能抑制P物质引起的内皮依赖性松弛。血管周围神经刺激使大脑动脉松弛，而使肠系膜动脉收缩；一氧化氮（NO）合酶抑制剂和肾上腺素能受体拮抗剂分别使松弛和收缩消失，表明大脑动脉和肠系膜动脉释放的神经递质主要为NO和去甲肾上腺素。尼卡地平、氟桂利嗪和AE0047对大鼠脑动脉神经源性松弛无影响，但对大鼠脑动脉神经源性松弛有抑制作用。虽然AE0047和尼卡地平均能抑制神经刺激和去甲肾上腺素引起的收缩，但神经刺激引起的去甲肾上腺素释放不受尼卡地平的抑制，而受AE0047的抑制。镉是一种非选择性钙拮抗剂，可抑制前列腺素F_<2alpha>、P物质和神经刺激的机械反应。这些结果表明，钙内流主要受血管平滑肌的L型通道和血管周围神经的N型通道调节，但在内皮细胞中的钙内流尚未确定，因为特异性的L、N和t型钙通道抑制剂未能抑制钙依赖的内皮功能。氟桂利嗪而非尼卡地平抑制神经源性脑动脉舒张可能解释其抗偏头痛作用。此外，还发现一些新的脱氢吡啶衍生物不仅具有直接的血管扩张作用，而且对交感神经功能有抑制作用。钙/钙调素依赖性蛋白激酶II参与神经NO的产生也被提出。少

Effects of calcium antagonists on the mechanical responses of isolated dog artery strips to the direct vasoconstrictor (prostaglandin F_<2alpha>), EDRF releaser (substance P) and nerve stimulation were examined. Contraction induced by prostaglandin F_<2alpha> was inhibited by nicardipine (L-type calcium channnel inhibitor), flunarizine and AE0047 (a new dihydropyridine derivative), but not by omega-conotoxin (N-type channel inhibitor). Endothelium-dependent relaxation caused by substance P was not suppressed by nicardipine, omega-conotoxin nor tetramethrin (T-type channel inhibitor). Perivascular nerve stimulation produced relaxations in the cerebral artery whereas contractions in the mesenteric artery ; the relaxation and contraction were abolished by nitric oxide (NO) synthase inhibitors and alpha-adrenoceptor antagonists, respectively, indicating that neurotransmitters mainly released from the cerebral and mesenteric arteries are NO and noradrenaline, respectively. Nicardipine and t … More etramethrin did not affect the neurogenic relaxation in the cerebral artery, but omega-conotoxin, flunarizine and AE0047 inhibited the relaxation. Although contractions induced by nerve stimulation and noradrenaline were suppressed by both AE0047 and nicardipine, noradrenaline release caused by nerve stumulation was not inhibited by nicardipine but by AE0047. Cadmium, a non-selective calcium antagonist, inhibited the mechanical responses to prostaglandin F_<2alpha>, substance P and nerve stimulation. These results indicate that calcium influx is mainly regulated by L-type channel in the vascular smooth muscles and by N-type channel in the perivascular nerves, but that in the endothelial cells has not been determined since specific L-, N- and T-type calcium channel inhibitors failed to inhibit the calcium-dependent endothelial function. Suppression by flunarizine, but not by nicardipine, of the neurogenic cerebroarteial relaxation may explain its anti-migraine action. Further, it is found that some of the new dehydropyridine derivatives possess not only direct vasodilator action but also inhibitory action on sympathetic nerve function. Involvement of calcium/calmodulin-dependent protein kinase II in the production of neural NO has also been suggested. Less