CALMIDAZOLIUM, A CALMODULIN INHIBITOR, INHIBITS ENDOTHELIUM-DEPENDENT RELAXATIONS RESISTANT TO NITRO-L-ARGININE IN THE CANINE CORONARY-ARTERY

被引:51
作者
ILLIANO, S [1 ]
NAGAO, T [1 ]
VANHOUTTE, PM [1 ]
机构
[1] BAYLOR COLL MED,CTR EXPTL THERAPEUT,HOUSTON,TX 77030
关键词
NITRIC OXIDE; ENDOTHELIUM-DERIVED HYPERPOLARIZING FACTOR; CALMIDAZOLIUM; CALMODULIN; CORONARY ARTERY; NITRO-L-ARGININE;
D O I
10.1111/j.1476-5381.1992.tb12756.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 The role of calmodulin in endothelium-dependent relaxations in the canine coronary artery, was investigated by use of the inhibitor of calmodulin, calmidazolium. 2 The endothelium-dependent relaxations to adenosine diphosphate (ADP) and nebivolol, a beta-adrenoceptor antagonist, in control solution, and to bradykinin in high potassium solution (to inhibit endothelium-dependent hyperpolarization), were abolished by nitro-L-arginine (30 muM), an inhibitor of nitro oxide-synthase. Calmidazolium (10 muM) did not inhibit these relaxations. 3 Calmidazolium did not affect the endothelium-independent relaxations to SIN-1, an exogenous donor of nitric oxide (NO). 4 The relaxations to bradykinin and to the calcium ionophore A23187 in control solution were inhibited to a small extent by calmidazolium (10 muM). 5 Bradykinin and A23187 induced relaxations in the presence of nitro-L-arginine (30 muM) that were abolished by calmidazolium (10 muM) but not affected by glibenclamide (10 muM), an inhibitor of ATP-sensitive K+ channels. 6 The endothelium-independent relaxations to lemakalim, an ATP-sensitive K+ channel opener, were not affected by calmidazolium (10 muM) but were inhibited by glibenclamide (10 muM). 7 These results suggest that calmidazolium does not inhibit the endothelium-dependent relaxations due to endothelium-derived NO in the canine coronary artery but inhibits either the production of endothelium-derived hyperpolarizing factor (EDHF) from endothelial cells or its effects on vascular smooth muscle cells. Furthermore these results suggest that EDHF contributes to endothelium-dependent relaxations in the canine coronary artery.
引用
收藏
页码:387 / 392
页数:6
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