Pacing-Induced Heart Failure in the Dog: Evaluation of Peripheral Vascular α-Adrenoceptor Subtypes

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Abstract
Summary: Postjunctional a-adrenoceptor characteristics were evaluated in canine dorsal pedal arterial and saphenous vein rings studied before and after development of severe pacing-induced heart failure (CHF). Before CHF, all agonists produced concentration-dependent increases in tension of both blood vessels. After development of CHF, the responsiveness and sensitivity of the vessels to the α1-agonists and the mixed agonists were significantly increased as compared with control. The maximum responses to BHT 920 and BHT 933 remained unaltered after CHF, but both vessels showed decreased sensitivity to BHT 920. Before CHF, the rank order of potency with respect to norepinephrine (NE) for the dorsal pedal artery was as follows: NE > epinephrine > methoxamine > BHT 933 > BHT 920, and for the saphenous vein was epinephrine > NE > BHT 933 > methoxamine > BHT 920. At peak CHF, the rank order of potency for the artery was epinephrine > NE> methoxamine > BHT 933 > BHT 920, whereas in the vein BHT 920 was ˜80 times less potent than NE (as compared with being only five times less potent before CHF). Prazosin was a potent, competitive antagonist (pA2 values of 9.2 and 9.0 for the artery and the vein) of methoxamine-induced contractions before development of CHF. Prazosin had a 10-fold lower potency against epinephrine-induced contractions in the dorsal pedal artery, whereas it was not competitive against epinephrine in the saphenous vein. Against the selective α2-aragonists, prazosin either showed no antagonism or was not competitive. After CHF, prazosin was non competitive against all agonists tested. Yohimbine was a potent, competitive antagonist against BHT 920 both before and at CHF. Yohimbine had intermediate antagonism against epinephrine and produced no antagonism of methoxamine-induced contractions. We conclude that increased reactivity and sensitivity of the peripheral vasculature to α1-agonists occurs at CHF

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