Pacing-induced heart failure in the dog: evaluation of peripheral vascular alpha-adrenoceptor subtypes.
Postjunctional alpha-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 alpha 1-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 greater than epinephrine greater than methoxamine greater than BHT 933 greater than BHT 920, and for the saphenous vein was epinephrine greater than NE greater than BHT 933 greater than methoxamine greater than BHT 920. At peak CHF, the rank order of potency for the artery was epinephrine greater than NE greater than methoxamine greater than BHT 933 greater than BHT 920, whereas in the vein BHT 920 was approximately 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 alpha 2-agonists, 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 alpha 1-agonists occurs at CHF.
Forster, C; Armstrong, PW
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