In vitro effects of desoxycorticosterone on vascular smooth muscle.
We present evidence in accord with the observations of S. Kalsner (Br. J. Pharmacol. 36: 582-593, 1969) that in the rabbit aorta, desoxycorticosterone (DOC) potentiates the contractile response to certain catecholamines by inhibiting their degradation by catechol-O-methyltransferase. In contrast, DOC depresses the contractile responses in rat aorta and tail arteries. To elucidate the mechanism of this depression the effect of DOC was evaluated under various conditions. DOC depressed the contractile response to epinephrine, phenylephrine, KCl, and angiotensin II. The depression was unaltered by ouabain or by a potassium-free solution, indicating that DOC did not produce its depression by altering Na-K-ATPase activity. The depression is unaltered in a chloride-free solution, demonstrating that the DOC effect is not caused by a change in membrane permeability to chloride. Radioisotope studies demonstrate that DOC does not alter membrane permeability to potassium. Removal of extracellular calcium with EGTA (ethylene glycol-bis (beta-aminoethyl ether) N, N'-tetraacetic acid) significantly reduced the magnitude of the DOC depression. Indirect evidence is presented suggesting that DOC might increase calcium binding to the plasma membrane, resulting in its stabilization and hence in a depression of the contractile response.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta; D001158:Arteries; D003900:Desoxycorticosterone / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D010042:Ouabain / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits
D000804:Angiotensin II; D010656:Phenylephrine; D003900:Desoxycorticosterone; D010042:Ouabain; D011189:Potassium Chloride; D011188:Potassium; D004837:Epinephrine