Ohashi K, Yamazaki J, Nagao T
Department of Toxicology and Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Eur J Pharmacol. 1995 Oct 16;285(2):165-71. doi: 10.1016/0014-2999(95)00403-8.
In order to investigate the effects of Ca2+, Ba2+ and Sr2+ on vascular endothelial nitric oxide (NO) production, contractile and relaxant responses of porcine depolarized coronary arteries to these divalent cations were compared. In the presence of diltiazem, Ba2+ induced NO-dependent relaxation, Sr2+ did slightly and Ca2+ did not; however all three cations increased cGMP levels in endothelium-intact arteries to similar extents. In the absence of diltiazem, these cations evoked contractions: the EC50 of Ca2+ for endothelium-denuded arteries was lower than those of Ba2+ and Sr2+. The IC50 of diltiazem for arteries precontracted with Ca2+ was higher than for arteries precontracted with Ba2+ and Sr2+. These results suggest that Ba2+ and Sr2+, as well as Ca2+, activate coronary arterial NO production, and also that the different responses of coronary arteries to these divalent cations can be explained, in part, by the different sensitivities of the smooth muscle to these cations and by the different potencies of diltiazem to inhibit the contractions the cations induced.
为了研究Ca2+、Ba2+和Sr2+对血管内皮一氧化氮(NO)生成的影响,比较了猪去极化冠状动脉对这些二价阳离子的收缩和舒张反应。在存在地尔硫䓬的情况下,Ba2+诱导NO依赖性舒张,Sr2+有轻微作用,而Ca2+则无此作用;然而,所有这三种阳离子均使完整内皮动脉中的环鸟苷酸(cGMP)水平升高至相似程度。在不存在地尔硫䓬的情况下,这些阳离子引起收缩:去内皮动脉对Ca2+的半数有效浓度(EC50)低于对Ba2+和Sr2+的。地尔硫䓬对Ca2+预收缩动脉的半数抑制浓度(IC50)高于对Ba2+和Sr2+预收缩动脉的。这些结果表明,Ba2+、Sr2+以及Ca2+均可激活冠状动脉NO的生成,并且冠状动脉对这些二价阳离子的不同反应,部分可通过平滑肌对这些阳离子的不同敏感性以及地尔硫䓬抑制这些阳离子诱导的收缩的不同效力来解释。