NIFEDIPINE INHIBITS RESPONSES TO ALPHA-ADRENOCEPTOR STIMULATION IN CANINE BLOOD-VESSELS - IMPACT OF HEART-FAILURE

The effects of nifedipine (10(-8) and 10(-7) M) on a-adrenergic responses of the dorsal pedal artery and saphenous vein were examined from dogs with pacing-induced heart failure. Two groups of dogs had their right ventricles paced at 250 beats/min: group (1) 1 week of pacing (mild heart failure) and group (2) paced for a mean period of 25.8 days (peak heart failure). Nifedipine non-competitively antagonised 6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]azepin dihydrochloride (BHT 920)-induced contractions to the same extent (i.e. at control, mild heart failure and peak heart failure) and IC50 values were as follows: for dorsal pedal artery 3.9 (1.8-6.1) nM, 4.4 (1.2-8.4) nM and 8.5 (2.9-38.9) nM, respectively; for saphenous vein 13.0 (4.6-26.0) nM, 13.0 (7.3-18.6) nM and 19.0 (9.3-32.8) nM, respectively). Before the onset of pacing, nifedipine did not affect concentration-effect curves generated to noradrenaline or phenylephrine in either the artery or the vein. After 1 week of pacing, nifedipine (10(-7) M) inhibited contractions to noradrenaline in the artery and the vein (70 +/- 5% for the artery and 51 +/- 4% for the vein). Nifedipine had no effect on phenylephrine-induced contractions. At peak heart failure, nifedipine inhibited both noradrenaline and phenylephrine contractions. These results indicate that nifedipine is useful in differentiating contractile activity of vascular smooth muscle with respect to alpha-adrenoceptor agonism.