A CALCIUM AGONIST, BAY-K-8644, SUPPRESSES THE EMBRYOTOXIC EFFECTS INDUCED BY DIHYDROPYRIDINES CALCIUM-CHANNEL BLOCKERS IN CULTURED RAT EMBRYOS

Day 9 rat embryos were exposed to 1,4-dihydropyridine calcium channel blockers; nifedipine (NIF), nicardipine (NIC) or nitrendipine (NIT), f or 48 hr in the whole embryo culture system. There were dose-dependent growth retardation and abnormalities, predominantly in cardiovascular system. The three compounds exhibited very similar pattern of dysmorp hogenic effects, but the potency of these compounds were quantitativel y different. The incidences of embryos with the abnormalities were 100 %, 100% and 85% Following either exposure of NIF, NIC or NIT at concen tration of 300, 8 and 15 mu M, respectively. This study was to investi gate whether these blocker-induced embryotoxicity was due to calcium c hannel blocking properties themselves in the embryos. Day 9 rat embryo s were co-exposed to 1,4-dihydropyridine calcium channel agonist, Bay k 8644 (BAY) and each calcium channel blocker under the same culture c ondition. The retarded embryonic growth induced by 200 or 300 mu M of NIF, 8 mu M Of NIC and 15 mu M of NIT nearly or completely ameliorated when embryos were co-exposed with BAY at one-third or half concentrat ion of each calcium channel blocker. Supplementation of BAY reduced th e incidence of abnormalities by NIF-, NIC- and NIT-alone. These result s suggested that one of mechanisms for embryotoxicity induced by calci um channel blocker was directly related to channel blocking properly o f the chemicals.