Angerbach D, Nicholson C D
Beecham-Wülfing Research Laboratories, Gronau, Federal Republic of Germany.
Naunyn Schmiedebergs Arch Pharmacol. 1988 Mar;337(3):341-6. doi: 10.1007/BF00168848.
The effect of Ca2+ antagonists, hydralazine and agents which enhance membrane K+ conductance (cromakalim, pinacidil and nicorandil) in smooth muscle cells, was compared on normal and hypoxic skeletal muscle blood cell flux and pO2. The K+ conductance enhancers and verapamil, diltiazem and nifedipine increased blood cell flux in normally perfused muscle. At equieffective blood pressure lowering dosages, the Ca2+ antagonists produced greater increases than the K+ channel openers. Hydralazine did not elevate blood cell flux in the normal muscle. In hypoxic skeletal muscle, the K+ conductance enhancers produced a marked increase in blood cell flux and in tissue oxygen tension, indicating that they had increased the nutritive blood flow in the muscle. The Ca2+ antagonists and hydralazine either did not change hypoxic muscle blood cell flux and pO2 or reduced them. The dissimilarity in the activity of the compounds may be due to differences in their site of action in the vascular bed. Ca2+ antagonists and hydralazine are known to reduce arteriolar vessel resistance and do not increase blood flow in hypoxic skeletal muscle. The positive effect of cromakalim, pinacidil and nicorandil may be due to relaxant activity on larger arterial blood vessels including collaterals. This effect could be related to their ability to enhance membrane K+ conductance in vascular smooth muscle cells.
比较了钙离子拮抗剂、肼屈嗪以及增强细胞膜钾离子电导的药物（克罗卡林、匹那地尔和尼可地尔）对正常和缺氧骨骼肌血细胞流量及氧分压的影响。钾离子电导增强剂以及维拉帕米、地尔硫䓬和硝苯地平可增加正常灌注肌肉中的血细胞流量。在等效降压剂量下，钙离子拮抗剂比钾离子通道开放剂能使血细胞流量增加得更多。肼屈嗪不会提高正常肌肉中的血细胞流量。在缺氧骨骼肌中，钾离子电导增强剂可使血细胞流量和组织氧张力显著增加，这表明它们增加了肌肉中的营养性血流。钙离子拮抗剂和肼屈嗪要么不会改变缺氧肌肉的血细胞流量和氧分压，要么会使其降低。这些化合物活性的差异可能归因于它们在血管床中作用部位的不同。已知钙离子拮抗剂和肼屈嗪可降低小动脉血管阻力，且不会增加缺氧骨骼肌中的血流量。克罗卡林、匹那地尔和尼可地尔的积极作用可能归因于它们对包括侧支血管在内的较大动脉血管的舒张活性。这种作用可能与其增强血管平滑肌细胞膜钾离子电导的能力有关。
