Effect of benzothiadiazine derivatives on cyclic nucleotide phosphodiesterase and on the tension of the aortic strip.
Effect of benzothiadiazine derivatives on cyclic nucleotide phosphodiesterase and on the tension of the aortic strip.
复制标题
苯并噻二嗪衍生物对环核苷酸磷酸二酯酶和主动脉带张力的影响。
DOI：
10.1159/000158238
复制
发表时间：
1980
期刊：
影响因子：
--
通讯作者：
L. Triner
中科院分区：
文献类型：
--
作者：
Y. Vulliemoz;M. Verosky;L. Triner
二氮嗪和氯噻嗪（0.1- 1.5 mM）对500 g大鼠主动脉匀浆上清液中测定的cAMP和cGMP水解速率具有剂量依赖性抑制作用;这两种化合物对cAMP和cGMP水解的抑制作用弱于茶碱。在二氮嗪或氯噻嗪存在下，主动脉的cAMP和cGMP含量没有变化;然而，二氮嗪进一步增加了异丙肾上腺素诱导的cAMP升高，而氯噻嗪没有。两种苯并噻二嗪均能降低5-羟色胺、苯丙氨酸或钾诱导的主动脉条最大张力。与茶碱相比，二氮嗪是一种较强的收缩反应抑制剂，氯噻嗪是一种较弱的收缩反应抑制剂。二氮嗪和氯噻嗪的生化和功能作用的比较表明，这些化合物对环核苷酸磷酸二酯酶的抑制作用本身并不能解释其血管舒张作用。
Diazoxide and chlorothiazide (0.1--1.5 mM) had a dose-dependent inhibitory effect on the rate of cAMP and cGMP hydrolysis determined in a 500-g supernatant of rat aorta homogenates; both compounds were weaker inhibitors of cAMP and cGMP hydrolysis than theophylline. cAMP and cGMP content of the aorta did not change in the presence of diazoxide or chlorothiazide; diazoxide, however, further increased the isoproterenol-induced rise in cAMP, while chlorothiazide did not. Both benzothiadiazines decreased the maximum tension of the aortic strip induced by serotonin, phenylephrine or potassium. Diazoxide was a stronger and chlorothiazide a weaker inhibitor of the contractile response than theophylline. Comparison of the biochemical and functional effects of diazoxide and chlorothiazide indicates that the inhibitory effect of these compounds on cyclic nucleotide phosphodiesterase does not by itself explain their vasodilating effect.