Moreland S, McMullen D M
Bristol-Myers Squibb Pharmaceutical Research Institute, Department of Pharmacology, Princeton, New Jersey 08543.
J Cardiovasc Pharmacol. 1990 Oct;16(4):609-15. doi: 10.1097/00005344-199010000-00012.
The vasorelaxant activity of SQ 31,765 and diltiazem was studied in intact and Triton X-100 detergent-skinned fibers of the swine carotid media. Both calcium channel blockers were used to relax or prevent contractions induced by depolarization with 110 mM KCl. The potencies of SQ 31,765 and diltiazem were similar for relaxing or preventing the tonic component of KCl-induced contractions of intact vascular smooth muscle strips. A significantly higher concentration of either compound was required to prevent the phasic component of the contraction. The possible direct effects of these calcium channel blockers on contractile function were examined in the detergent-skinned carotid medial fiber contracted with 3 microM Ca2+. Both stress and myosin light chain (MLC) phosphorylation levels were determined in detergent-skinned fibers in the presence and absence of the channel blockers. Neither compound affected stress or MLC phosphorylation in Ca2(+)-contracted detergent-skinned fibers, indicating a lack of direct effect on the contractile proteins. Thus, SQ 31,765 appears to act selectively at the level of the sarcolemma.
在猪颈动脉中层的完整纤维和经Triton X - 100去污剂处理的去表皮纤维中研究了SQ 31,765和地尔硫䓬的血管舒张活性。两种钙通道阻滞剂均用于舒张或预防由110 mM氯化钾去极化诱导的收缩。SQ 31,765和地尔硫䓬在舒张或预防完整血管平滑肌条氯化钾诱导收缩的强直成分方面效力相似。预防收缩的相性成分需要显著更高浓度的任一化合物。在与3 microM Ca2+收缩的经去污剂处理的颈动脉中层纤维中研究了这些钙通道阻滞剂对收缩功能的可能直接作用。在有和没有通道阻滞剂的情况下，在经去污剂处理的纤维中测定应力和肌球蛋白轻链（MLC）磷酸化水平。两种化合物均未影响Ca2(+)-收缩的经去污剂处理的纤维中的应力或MLC磷酸化，表明对收缩蛋白缺乏直接作用。因此，SQ 31,765似乎选择性地作用于肌膜水平。
