Intracellular angiotensin II regulates the inward calcium current in cardiac myocytes.
-The influence of intracellular administration of angiotensin II (Ang II) on the inward calcium current (ICa) was investigated in single myocytes isolated from adult rat ventricle. Comparative studies were also made in ventricular cells of Golden hamsters. The ICa 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 ICa 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 [Sar1Val5Ala8] Ang II (10(-6) mmol/L) did not change the effect of Ang II. Stimulation of ICa by exogenous cAMP or inhibition of protein kinase C did not alter the effect of Ang II on ICa. Zaprinast (100 micromol/L), an inhibitor of cGMP phosphodiesterase, when added to the bath solution increased appreciably the effect of Ang II on ICa (P<0.05). In ventricular myocytes of Golden hamsters, in which Ang II has a positive inotropic action, the intracellular administration of Ang II (10(-8) mmol/L) increased ICa 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 [Sar1Val5Ala8] 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 ICa in the hamster myocytes. The results particularly suggest that the activation of the cardiac renin-angiotensin system regulates ICa and myocardial contractility, an effect that varies with the species.
De Mello
W C
WC
Departments of Pharmacology and Anesthesiology, School of Medicine, University of Puerto Rico, San Juan 00936-5067.
D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006224:Cricetinae; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles; D019808:Losartan / Q000494:pharmacology; D008647:Mesocricetus; D008845:Microinjections; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012084:Renin-Angiotensin System; D013045:Species Specificity; D013997:Time Factors
D057911:Angiotensin Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D011493:Protein Kinase C; D019808:Losartan; D002118:Calcium