Intracellular angiotensin II regulates the inward calcium current in cardiac myocytes

被引:102
作者
De Mello, WC
机构
[1] Univ Puerto Rico, Sch Med, Dept Pharmacol, San Juan, PR 00936 USA
[2] Univ Puerto Rico, Sch Med, Dept Anesthesiol, San Juan, PR 00936 USA
关键词
angiotensin II; intracellular; calcium current; myocytes;
D O I
10.1161/01.HYP.32.6.976
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
The influence of intracellular administration of angiotensin II (Ang LI) on the inward calcium current (I-Ca) was investigated in single myocytes isolated from adult rat ventricle. Comparative studies were also made in ventricular cells of Golden hamsters, The I-Ca was measured in single cells using the whole-cell voltage clamp configuration. The results indicated that Ang II (10(-8) mmol/L) dialyzed into the rat myocytes reduced the peak I-Ca by 35+/-5.5% (n=20; P<0.05), Losartan (10(-7) mmol/L) added to the bath did not suppress the effects of Ang II, indicating that the peptide is acting intracellularly. Moreover, the intracellular dialysis of losartan (10(-6) mmol/L) or [Sar(1)Val(5)Ala(8)] Ang II (10(-6) mmol/L) did not change the effect of Ang II. Stimulation of I-Ca by exogenous cAMP or inhibition of protein kinase C did not alter the effect of Ang II on I-Ca. Zaprinast (100 mu mol/L), an inhibitor of cGMP phosphodiesterase, when added to the bath solution increased appreciably the effect of Ang II on I-Ca (P<0.05). In ventricular myocytes of Golden hamsters, in which Ang II has a positive inotropic action, the intracellular administration of Ang LT (10(-8) mmol/L) increased I-Ca by 36+/-2.4% (n=20; P>0.05). The effect of the peptide was not altered by the intracellular administration of losartan (10(-6) mmol/L), by [Sar(1)Val(5)Ala(8)] Ang II (10(-6) mmol/L), or by the inhibitor of protein kinase A. The inhibition of protein kinase C, however, prevented the effect of Ang II I-Ca in the hamster myocytes, The results particularly suggest that the activation of the cardiac renin-angiotensin system regulates I-Ca and myocardial contractility, an effect that varies with the species.
引用
收藏
页码:976 / 982
页数:7
相关论文
共 25 条
[1]   ANGIOTENSIN-II INCREASES SPONTANEOUS CONTRACTILE FREQUENCY AND STIMULATES CALCIUM CURRENT IN CULTURED NEONATAL RAT-HEART MYOCYTES - INSIGHTS INTO THE UNDERLYING BIOCHEMICAL-MECHANISMS [J].
ALLEN, IS ;
COHEN, NM ;
DHALLAN, RS ;
GAA, ST ;
LEDERER, WJ ;
ROGERS, TB .
CIRCULATION RESEARCH, 1988, 62 (03) :524-534
[3]   THE CARDIAC RENIN-ANGIOTENSIN SYSTEM - ITS POSSIBLE ROLE IN CELL COMMUNICATION AND IMPULSE PROPAGATION [J].
DEMELLO, WC .
CARDIOVASCULAR RESEARCH, 1995, 29 (06) :730-736
[4]   IS AN INTRACELLULAR RENIN-ANGIOTENSIN SYSTEM INVOLVED IN CONTROL OF CELL COMMUNICATION IN HEART [J].
DEMELLO, WC .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1994, 23 (04) :640-646
[5]   CARDIAC REFRACTORINESS IN RATS IS REDUCED BY ANGIOTENSIN-II [J].
DEMELLO, WC ;
CRESPO, MJ .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1995, 25 (01) :51-56
[6]   Renin-angiotensin system and cell communication in the failing heart [J].
deMello, WC .
HYPERTENSION, 1996, 27 (06) :1267-1272
[7]   THE EFFECTS OF ATRIOPEPTIN AND ANGIOTENSIN ON THE RAT RIGHT VENTRICLE [J].
DOGGRELL, SA .
GENERAL PHARMACOLOGY, 1989, 20 (02) :253-257
[8]   DETECTION OF ANGIOTENSIN-I AND ANGIOTENSIN-II IN CULTURED RAT CARDIAC MYOCYTES AND FIBROBLASTS [J].
DOSTAL, DE ;
ROTHBLUM, KN ;
CONRAD, KM ;
COOPER, GR ;
BAKER, KM .
AMERICAN JOURNAL OF PHYSIOLOGY, 1992, 263 (04) :C851-C863
[9]  
Dzau V J, 1988, Am J Med, V84, P22, DOI 10.1016/0002-9343(88)90201-X
[10]   IDENTIFICATION OF RENIN AND ANGIOTENSINOGEN MESSENGER-RNA SEQUENCES IN MOUSE AND RAT BRAINS [J].
DZAU, VJ ;
INGELFINGER, J ;
PRATT, RE ;
ELLISON, KE .
HYPERTENSION, 1986, 8 (06) :544-548