Vasodilatory effects of nifedipine, methoxyverapamil, and sodium nitroprusside on contractile responses of the ewe uterine artery at term pregnancy.

The differential inhibitory effect of the vasodilators on contractile responses to norepinephrine, serotonin, and potassium on isolated uterine artery ring segments from pregnant ewes within 2 weeks of term was quantified and correlated with the source of Ca++ for the vasoconstrictors producing the smooth muscle contraction. The contraction evoked by the vasoconstrictors was dependent on extracellular Ca++ and in agonist-induced contractions also on an intracellular pool of Ca++. Nifedipine effectively inhibited K(+)-induced (90 mmol/L) contractions (antagonist concentration to reduce the maximum contractile effect to the agonist to 50%, 1.95 +/- 0.9 x 10(-8) mol/L), whereas it was relatively ineffective in blocking norepinephrine-induced (10(-5) mol/L) or serotonin-induced (10(-5) mol/L) vasoconstriction (antagonist concentration to reduce the maximum contractile effect to the agonist to 50%, 1.38 +/- 0.4 x 10(-4) mol/L and 2.04 +/- 0.4 x 10(-5) mol/L, respectively). Methoxyverapamil (D-600) strongly inhibited serotonin-induced contractions (antagonist concentration to reduce the maximum contractile effect to the agonist to 50%, 3.3 +/- 0.3 x 10(-7) mol/L). The phasic rather than the tonic components of the serotonin- and norepinephrine-induced contractions were more effectively inhibited by D-600 (p less than 0.05). Sodium nitroprusside preferentially blocked (p less than 0.05) the sustained tonic components of norepinephrine- and serotonin-induced vasoconstrictions (antagonist concentration to reduce the maximum contractile effect to the agonist to 50%, 7.1 +/- 0.4 x 10(-7) mol/L and 8.2 +/- 0.6 x 10(-7) mol/L, respectively). On the basis of these findings it is concluded that D-600 and sodium nitroprusside are more effective than nifedipine in blocking contractile responses due to receptor stimulation, and therefore might be more effective in the treatment of hypertensive emergencies in which these amines might be implicated.