title: Calcium antagonists stimulate prostaglandin synthesis by cultured rat cardiac myocytes and prevent the effects of hypoxia.
abstract: The effect of three calcium antagonists on the synthesis of prostacyclin (PGI2, assayed as 6-Keto-PGF1 alpha) and PGE2 by cultured rat cardiac myocytes and fibroblasts was investigated. In myocytes only, bepridil, diltiazem and verapamil (10(-9) to 10(-7) M) stimulated PGs synthesis by two- to three-fold, dose-dependently. At a concentration of 10(-6) or 10(-5) M the intensity of the stimulation of PGI2 and PGE2 decreased. Cobalt chloride (2 X 10(-3) M) did not change PGs synthesis (pg/mg of protein/30 min; means +/- SE, N = 10; PGE2: 365 +/- 59 and 463 +/- 89 treated vs controls; PGI2: 824 +/- 214 and 799 +/- 143 treated vs controls). After 30 min exposure of myocytes to hypoxic conditions (glucose-free medium and low PO2), the glycogen content was half that of the controls (P less than 0.001), ATP content did not change and PGI2 and PGE2 synthesis increased (X1.5, P less than 0.05). When applied to myocytes 30 min before inducing hypoxia, the three calcium antagonists stimulated PGs synthesis by three- to seven-fold at maximal effect, and bepridil (10(-8) M) or diltiazem (10(-7) M) prevented the hypoxia-induced decrease in glycogen content. With 10(-5) M drug concentration, the effect on PGs was not significant, except for the effect of bepridil on PGI2 (P less than 0.05). It is concluded that therapeutic concentrations of calcium antagonists simultaneously prevent the decrease in myocyte glycogen induced by hypoxia and stimulate PGs synthesis by myocytes.
mesh_terms: D000818:Animals; D015764:Bepridil; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D003035:Cobalt / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D015232:Dinoprostone; D011464:Epoprostenol / Q000096:biosynthesis*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D000860:Hypoxia / Q000188:drug therapy* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D011458:Prostaglandins E / Q000096:biosynthesis*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D011458:Prostaglandins E; D011759:Pyrrolidines; D003035:Cobalt; D015764:Bepridil; D006003:Glycogen; D014700:Verapamil; D011464:Epoprostenol; D004110:Diltiazem; C018021:cobaltous chloride; D015232:Dinoprostone