Chloroethylclonidine and alpha-adrenoceptor agonist interaction in blood vessels following heart failure

This study examined the interaction of chloroethylclonidine with alpha-adrenoceptor agonists in canine endothelium-denuded dorsal pedal artery and saphenous vein before (non-paced) and at end-stage heart failure which was induced by rapid ventricular pacing (250 bpm for no more than four weeks). The interaction was heterogeneous in both non-paced and heart failure blood vessels. In the dorsal pedal artery, only chloroethylclonidine (10(-4) M) reduced the maximum response to noradrenaline. At 10(-6) and 10(-5) M, chloroethylclonidine potentiated the response to noradrenaline. In the saphenous vein, chloroethylclonidine was not surmountable against noradrenaline before heart failure, but produced competitive antagonism of noradrenaline in the heart failure group (pA2 = 5.7). In the dorsal pedal artery, chloroethylclonidine potentiated the response to low concentrations of methoxamine, but inhibited the response of higher concentrations. In the saphenous vein, chloroethylclonidine (10(-6) and 10(-5) M) potentiated the response to methoxamine from non-paced dogs but did not significantly effect the response at heart failure. In the dorsal pedal artery, chloroethylclonidine (10(-4) M) potentiated low concentrations and inhibited higher concentrations of phenylephrine from non-paced animals but had no significant effect at heart failure. In contrast, in the saphenous vein, chloroethylclonidine (at all concentrations tested) inhibited the response to phenylephrine in non-paced dogs, whereas the inhibitory effect was not as marked in heart failure. In conclusion, these results indicate that differences in alpha1-adrenoceptor populations and distribution are blood vessel dependent and dependent on the pathological state.