title: Mechanism for the postive inotropic effect of angiotensin II on isolated cardiac muscle.
abstract: Angiotensin II (A II) and analogues were tested for their ability to restore electrical and mechanical activity to cardiac muscle preparations in which the fast Na+ channels had been inactivated by partial depolarization (22-27 mM K+) or by tetrodotoxin (TTX). The partially depolarized or TTX-blocked preparations were chosen because under these conditions electrical and mechanical responses are primarily Ca2+ -dependent. In depolarized rabbit right atria, A II restored spontaneous mechanical and electrical activity (measured by both intracellular and extracellular recording techniques). The frequency of action potential discharge was concentration-dependent; the threshold concentration of A II was 10(-10) M, the ED50 was 8 X 10(-9) M, and the maximum effect was observed at 5 X 10(-8) M. In contrast, depolarized guinea pig atria were insensitive to A II, Sar1-angiotensin II, and des-Asp1-angiotensin II, even at concentrations as high as 10(-5) M. Rabbit papillary muscle (TTX-blocked), embryonic (18-day) chick heart (partially depolarized) and chick heart reaggregates (TTX-blocked) responded similarly to rabbit atria in that A II (9.6 X 10(-7) M) restored both electrical and mechanical activity. We found that in these preparations the action of A II was unaffected by propranolol (5.0 X 10(-6) M to 5.0 X 10(-5) M) but was blocked by Mn2+ (10(-3) M), D-600 (1 X 10(-7) g/ml) and the specific A II antagonists Sar1-Ala8-angiotensin II (P-113) (5.0 X 10(-5) M) and Sar1-Ile8-angiotensin II (5.28 X 10(-5) M). We conclude that the positive inotropic effect of A II on the myocardium is due to its ability to increase transmembrane ion movements in or through the cell membrane. The ability of Mn2+ and D-600 to block this effect suggests that this ion movement is via the so-called "slow channels."
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D002642:Chick Embryo; D004837:Epinephrine / Q000494:pharmacology; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D008345:Manganese / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D013268:Stimulation, Chemical; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D000804:Angiotensin II; D008345:Manganese; D013779:Tetrodotoxin; D011433:Propranolol; D009638:Norepinephrine; D004837:Epinephrine