alpha(1D)-Adrenoceptors do not contribute to inotropic responses of neonatal rat myocardium

This study investigated the role of alpha(1D)-adrenoceptors (ARs) in the inotropic responses of neonatal (7-day-old) rat myocardium by using the relatively selective antagonist BMY 7378. The positive inotropic effects of phenylephrine on right ventricular strips of neonatal rats were not inhibited by BMY 7378 up to a concentration of 300 nM but potently antagonized by the alpha(1)AR antagonist 5-methylurapidil (5-MU) (pK(B), 8.73+/-0.12; n=6). BMY 7378 was similar to 1,000-fold less potent (pK(i), 6.63+/-0.7; n=5) in inhibiting the binding of [H-3]prazosin to right ventricular membrane preparations of neonatal rats than was 5-MU (pK(i), 9.04+/-0.54; n=5). Neonatal rat cerebral cortex and adult rat aorta were used as additional controls. BMY 7378 was a weak inhibitor of [H-3]prazosin binding to neonatal cortex (pK(i), 6.8+/-0.04; n=3) but highly potent in inhibiting the binding to adult rat aortic membrane preparations (pK(i) for high-affinity binding, 9.70+/-0.30; n=4); BMY 7378 potently antagonized the effects of phenyleprine on adult rat aortic strips (pK(B), 9.05+/-0.11; n=5). It is concluded that alpha(1D)ARs do not play a significant role in alpha(1)AR-mediated inotropic responses of neonatal rat myocardium.