A pharmacological study of the rabbit saphenous artery in vitro: a vessel with a large purinergic contractile response to sympathetic nerve stimulation.

Abstract

Mechanical responses to transmural electrical stimulation were recorded in isolated transverse ring preparations of rabbit saphenous artery. Electrical stimulation for a period of 1 s produced a rapid monophasic contraction and, for a period of 1 min, a biphasic contraction consisting of a rapid constriction followed by a slower sustained constriction. All contractions were abolished in the presence of tetrodotoxin (1 microgram ml-1) or guanethidine (4 microM). After desensitization of the P2-purinoceptor with alpha,beta-methylene ATP, contractions to electrical stimulation for 1 s were reduced significantly at all frequencies tested: responses evoked by stimulation at 4 Hz were usually almost completely inhibited, whereas those evoked by stimulation at 64 Hz were only partially inhibited. On the other hand, in the presence of the alpha-adrenoceptor antagonist, prazosin, neurogenic contractions were only partially reduced: at 4 Hz there was no significant reduction in the neurogenic contractions while at 32 and 64 Hz, contractions were reduced by an average of 20 and 28% respectively. Usually all contractions were abolished by a combination of the two drugs. Prazosin antagonized contractions of the vessel to exogenously applied noradrenaline but not to ATP, whereas desensitization of the P2-purinoceptor with alpha,beta-methylene ATP blocked responses to ATP but not those to noradrenaline. The concentration response curve to histamine was not affected by treatment of the vessel with prazosin, or after desensitization of the P2-purinoceptor with alpha,beta-methylene ATP. These results suggest that noradrenaline and ATP are co-released from sympathetic nerves supplying the rabbit saphenous artery, both substances being involved in the mechanical contractions of this tissue. Further, the ratio of ATP to noradrenaline involved in these mechanical contractions is dependent upon the frequency of stimulation, but at all frequencies tested the purinergic component is greater than the adrenergic component.