EFFECTS OF NIFEDIPINE AND BAY-K-8644 ON MYOTROPIC RESPONSES IN AORTICRINGS OF PREGNANT RATS

The hypothesis that Ca2+ channel function is altered during pregnancy was tested by comparing responses to potassium chloride (KCl) and phen ylephrine in aortic rings of virgin and term-pregnant rats under the i nfluence of nifedipine and Bay K 8644. Maximum response to KCl was pro gressively reduced by increasing nifedipine concentrations (1.0-100 nM ) in both groups of tissues. Nifedipine produced a smaller inhibition of KCl-induced contraction in aortic rings of pregnant than of virgin rats. It exerted little inhibition on the concentration-response curve to phenylephrine. The Ca2+ channel antagonist (100 nM) reduced the ma ximum response to the alpha-adrenoceptor agonist in rings from virgin rats, but had no effect in pregnant rats. Bay K 8644, a Ca2+ channel a ctivator, potentiated the responses to low concentrations of both phen ylephrine and KCl in the tissues of both virgin and pregnant rats, but did not affect maximum responses. It also induced concentration-depen dent contractions in rings of virgin but not of pregnant rats. The eff ects of Bay K 8644 were markedly potentiated by precontracting the aor ta with 10 mM KCl. Nevertheless tissues from pregnant rats were still less responsive to Bay K 8644. However, when the strips were precontra cted to the same level by different concentrations of KCl, the concent ration-response curves to Bay K 8644 were identical in both groups: [H -3]Nitrendipine binding to membrane preparations of the thoracic aorta was similar in virgin and. pregnant rats. These results show that the effects of both nifedipine and Bay K 8644 were decreased in aortic ri ngs of pregnant compared to virgin rats and indicate that potential-op erated Ca2+ channel function is altered in the aorta of pregnant rats. Furthermore, it is suggested that modulation of membrane potential wi th KCl can reverse this change.