ALPHA(1D)-ADRENOCEPTORS DO NOT CONTRIBUTE TO INOTROPIC RESPONSES OF NEONATAL RAT MYOCARDIUM

This study investigated the role of alpha(1D)-adrenoceptors (ARs) in t he 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 pot ently 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 po tent (pK(i), 6.63+/-0.7; n=5) in inhibiting the binding of [H-3]prazos in to right ventricular membrane preparations of neonatal rats than wa s 5-MU (pK(i), 9.04+/-0.54; n=5). Neonatal rat cerebral cortex and adu lt rat aorta were used as additional controls. BMY 7378 was a weak inh ibitor 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 adul t rat aortic strips (pK(B), 9.05+/-0.11; n=5). It is concluded that al pha(1D)ARs do not play a significant role in alpha(1)AR-mediated inotr opic responses of neonatal rat myocardium.