Analysis of effects of Ca-antagonists in pathophysiological models

Ca2+拮抗剂在病理生理模型中的作用分析

• 批准号: 04454530
• 负责人: NAGAO Taku
• 金额: $ 4.29万
• 依托单位: University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454530/
• 关键词: Ca^<2+>antagonist; Ca^<2+>channel; Ca^<2+> current; diltiazem; nifedipine; verapamil; hypertension; ischemia; 心筋; パッチクランプ; 高血圧自然発症ラット; 大動脈

An analysis of the mechanism of Ca antagonists was studied in the pathological model condition.(1) The number of Ca channels in aortas of SHR and WKY rats are not significantly different, even when hypertension is established in SHR.(2) The effects of diltiazem and its quaternary derivatives on ICa(L) in isolated ventricular myocytes were studied in normal and different pH conditions. We found that diltiazem acts from outside of the membrane.(3) The effects of elevation of extracellular K+ concentration on the negative inotropic potencies of Ca antagonists were investigated in guinea-pig ventricular muscle. We found that the differential effects of the Ca antagonists are explained by the differences in voltage dependency of their use-dependent blocking effects on ICa(L).

（1）SHR和WKY大鼠主动脉中的CA通道的数量也没有显着差异，即使在SHR中建立高血压（2）diltiazem及其Quaternary Quaternary衍生物对ICA（L）对分离的杂化肌细胞对ica（L）的影响，对CA拮抗剂的机制的分析也没有显着差异。我们发现，diltiazem起源于膜外。（3）在几内亚猪心室肌肉中研究了细胞外K+浓度升高对Ca拮抗剂负性肌力效应的影响。我们发现，CA拮抗剂的差异效应是通过其使用依赖性阻断对ICA（L）的电压依赖性依赖性的差异来解释的。

项目成果

R.Okuyama: "Effect of K^+-depolarization on the potency of Ca^2 antagonists in the guinea-pig isolated papillary muscle" The Japanese Journal of Pharmacology. 58. 189 (1992)

R.Okuyama：“K^-去极化对豚鼠离体乳头肌中 Ca^2 拮抗剂效力的影响”《日本药理学杂志》。

S.Adachi-Akahane: "Binding sites for diltiazem is on the extracellular side of the L-type Ca^<2+> channel" Circulation. 88(Supplement). I-230 (1993)

S.Adachi-Akahane：“地尔硫卓的结合位点位于 L 型 Ca^2 通道的细胞外侧”循环。

S.Ikeda, Y.Amano, S.Adachi-Akahane and T.Nagao: "Binding of (+)[^3H]PN200-110 to aortic and cardiac membranes from spontaneously hypertensive rats (SHR)in comparison with that from normotensive Wistar-Kyoto (WHY) rats." Jpn.H.J. 34. 532 (1993)

S.Ikeda、Y.Amano、S.Adachi-Akahane 和 T.Nagao：“与正常血压 Wistar 相比，( )[^3H]PN200-110 与自发性高血压大鼠 (SHR) 的主动脉和心脏膜的结合 -

S.Adachi-Akahane: "Binding sites for diltiazem is on the extracellular side of the L-type Ca^<2+>channel" Circulation(Supplement). 88. I-230 (1993)

S.Adachi-Akahane：“地尔硫卓的结合位点位于 L 型 Ca^2 通道的细胞外侧”循环（补充）。

T.Tanaka: "Synthesis of the optically active trans-isomers of diltiazem and their cardiovascular effects and Ca-antagonistic activity" Chemical and Pharmaceutical Bulletin. 40. 1476-1480 (1992)

T.Tanaka：“地尔硫卓光学活性反式异构体的合成及其心血管作用和 Ca 拮抗活性”化学和药物通报。