Calcium and angiotensin tachyphylaxis in rat uterine smooth muscle.
Studies were carried out to investigate the relationship between extracellular Ca++ and the ability of a particular smooth muscle to develop tachyphylaxis to angiotensin II (AII). Stimulation of rat uterus by AII was found to be dependent on extracellular Ca++. Placing the tissue in 0 Ca++ completely blocked AII-induced contractions as did the presence of the "Ca++ antagonists" verapamil (10- minus 5M), SKF 525-A (10- MINUS 5M), tetracaine (10- minus 4M), Mn++ (8 times 10- minus 3M), or La-3+ (10- minus 3M). In addition, it is no longer possible to produce tachyphylaxis to AII in deplorazed rat uterus under conditions of pH and Ca++ concentration in which a normally polarized preparation would be unresponsive. Verapamil, on the other hand, was an even more effective antagonist of AII in depolarized preparations (ID50 of 10- minus 8M) than in normal tissues (ID50 of 2.0 times 10- minus 7M). Like the rat uterus, the smooth muscle of the guinea pig ileum also develops tachyphylaxis to AII, and the effect of this peptide was also blocked by 10- minus 5 M verapamil. Rabbit aorta, however, was found to be relatively resistant to both development of tachyphylaxis under conditions of low Ca++ and low pH and also to inhibition by even very high concentrations of verapamil (10- minus 4M). The results of these studies suggest that the Ca++ site involved in the tachyphylactic response to AII may be a physiologically important one in those smooth muscles in which movement of extracellular Ca++ contributes to the inward ion currents during excitation. Verapamil, however, appears to act at a common step in the excitation-contraction sequence in rat uterus. A working model of the interaction of AII with rat uterine smooth muscle is presented.
D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D002118:Calcium / Q000008:administration & dosage / Q000494:pharmacology*; D004054:Diethylstilbestrol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000494:pharmacology; D005260:Female; D006863:Hydrogen-Ion Concentration; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007811:Lanthanum / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D051379:Mice; D008954:Models, Biological; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009215:Myometrium / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011335:Proadifen / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D013618:Tachyphylaxis; D013748:Tetracaine / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D013748:Tetracaine; D000804:Angiotensin II; D008345:Manganese; D007811:Lanthanum; D004054:Diethylstilbestrol; D004492:Edetic Acid; D011335:Proadifen; D014700:Verapamil; D000109:Acetylcholine; D002118:Calcium; D009638:Norepinephrine