Angiotensin converting enzyme and the arrhythmogenic action of angiotensin I: cardiac cell membrane as a site of angiotensin I conversion

被引:3
作者
De Mello, WC [1 ]
机构
[1] Univ Puerto Rico, Dept Pharmacol, San Juan, PR 00936 USA
关键词
angiotensin I; angiotensin converting enzyme; cardiac arrhythmias; inward calcium current; heart;
D O I
10.1016/j.regpep.2004.04.008
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The influence of angiotensin I (Ang I) on heart excitability and refractoriness was investigated in isolated right ventricular muscle of adult rats as well as in isolated ventricular myocytes. The results indicated that Ang I (10(-8) M) added to the bath solution, decreased the action potential duration from 50.4 +/- 3.6 to 33.9 +/- 3.9 ms (P < 0.05) and reduced significantly the cardiac refractoriness. Consequently, a discharge of spontaneous action potentials was elicited when a second stimulus was applied during the relative refractory period. Moreover, the conduction velocity was reduced from 56.9 +/- 2.9 to 40 +/- 3.2 cm/s (P < 0.05). The question whether the effect of Ang I was related to its conversion to Ang II, was investigated on tissues exposed to enalapril maleate (10(-8) M). Under these conditions, the effect of Ang I was totally suppressed. Similar results were found with losartan (10(-7) M). To investigate if the conversion of Ang I to Ang II occurs at the level of surface cell membrane. measurements of inward calcium current (I-Ca) were performed in myocytes isolated from the rat ventricle. I-Ca was measured before and after the administration of Ang I (10(-8) M). The results indicated that Ang I (10(-8) M), added to the bath solution, reduced the peak I-Ca density by 26.3 +/- 2.6% (P < 0.05), an effect abolished by enalapril maleate (10(-8) M). Conclusion: Evidence is presented for the first time, that Ang I is converted to Ang II at the surface cell membrane in cardiac muscle with consequent generation of cardiac arrhythmias which are elicited by Ang II. (C) 2004 Published by Elsevier B.V.
引用
收藏
页码:83 / 88
页数:6
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