Mechanisms of relaxant action of nicardipine, a new Ca++‐antagonist, on isolated dog cerebral and mesenteric arteries.
Mechanisms of relaxant action of nicardipine, a new Ca++‐antagonist, on isolated dog cerebral and mesenteric arteries.
复制标题
新型 Ca++ 拮抗剂尼卡地平对离体狗脑动脉和肠系膜动脉的松弛作用机制。
作者：
M. Yamamoto;T. Ohta;N. Toda
在用前列腺素(PG)F2α、碳环血栓素A2(CTxA2)或K+收缩的大脑和肠系膜动脉螺旋切条上，加入尼卡地平可引起剂量相关的松弛。用PGF2α和cTxA2收缩时，尼卡地平对脑动脉的松弛作用大于肠系膜动脉，但在K+收缩的动脉中差异不显著。尼卡地平对收缩的脑动脉和PGF2α也有类似程度的松弛作用。尼卡地平预处理可减弱对PGF2α的收缩反应，脑血管的收缩反应比肠系膜动脉的收缩反应更弱。在先前暴露于无钙介质并被过量K+去极化的脑动脉和肠系膜动脉上，钙离子引起的收缩被尼卡地平以相似的程度减弱。尼卡地平可减弱无钙介质中PGF2α引起的脑动脉收缩，而对肠系膜动脉的收缩无影响。尼卡地平对经PGF2α处理的脑动脉中钙离子诱导的收缩的减弱作用强于肠系膜动脉。结论：尼卡地平对脑动脉的舒张性大于肠系膜动脉，可能与其抑制Ca~(++)内流和减少细胞内钙离子的释放有关。就使用的浓度而言，尼卡地平似乎减弱了肠系膜动脉平滑肌细胞膜上钙离子的内移，但不抑制细胞内储存的钙离子的释放。
In helically-cut strips of cerebral and mesenteric arteries contracted with prostaglandin (PG) F2 alpha, carbocyclic thromboxane A2 (cTxA2) or K+, the addition of nicardipine caused a dose-related relaxation. Nicardipine-induced relaxation was greater in cerebral than in mesenteric arteries when contracted with PGF2 alpha and cTxA2, but did not appreciably differ in the arteries contracted with K+. Cerebral arteries contracted with hemolysate and PGF2 alpha relaxed in response to nicardipine to a similar extent. The contractile response to PGF2 alpha was attenuated by pretreatment with nicardipine, the attenuation being greater in cerebral than in mesenteric arteries. Ca++-induced contractions in cerebral and mesenteric arteries previously exposed to Ca++-free media and depolarized by excess K+ were attenuated by nicardipine to a similar extent. PGF2 alpha-induced contractions of cerebral arteries exposed to Ca++-free media were attenuated by nicardipine, whereas those of mesenteric arteries were unaffected. Attenuations by nicardipine of the Ca++-induced contraction in PGF2 alpha-treated cerebral arteries were greater than those seen in mesenteric arteries. It may be concluded that nicardipine produces a greater relaxation of cerebral arteries than mesenteric arteries, possibly due to a greater inhibition of the Ca++-influx and to a decrease in the release of Ca++ from intracellular storage sites in cerebral arteries. As far as the concentrations used are concerned, nicardipine appears to attenuate the inward movement of Ca++ across cell membrane in mesenteric arterial smooth muscle, but not the release of intracellularly stored Ca++.