Neurotransmitters and pre‐ and post‐junctional receptors involved in the vasoconstrictor response to sympathetic nerve stimulation in rat tail artery

Abstract

The study was prompted by the need to re-evaluate, in view of the complexity of the evidence in the literature, the relative roles of different sympathetic transmitters and receptors in the contractile response of the tail artery of adult normotensive rats to electrical field stimulation. By the pharmacological approach employed, noradrenaline and adenosine 5''-triphosphate appeared to contribute to this response; the possible roles of other putative transmitters such as neuropeptide Y could not be examined due to lack of specific antagonists. Noradrenaline, clearly the main mediator, exerted both excitatory and inhibitory effects, acting in part via different receptors depending on the stimulus parameters. Thus, yohimbine and prazosin (.alpha.2- and .alpha.1-adrenoceptor antagonists, respectively) were about equally effective as inhibitors of the noradrenaline-mediated contractile response to stimulation with short trains and/or at low frequency, but the response caused by long trains and/or high-frequency stimulation was much more strongly inhibited by prazosin than by yohimbine. As expected, yohimbine enhanced the [3H]noradrenaline overflow response to long but not to short stimulus trains, presumably because in the latter case the noradrenaline concentration in the relevant biophase was too low to activate the pre-junctional .alpha.2-adrenoceptors. Finally, propranolol, an unselective .beta.-adrenoceptor antagonist, enhanced the neurogenic contraction, indicating that noradrenaline restricts this response by effects via post-junctional .beta.-adrenoceptors. Adenosine triphosphate appeared to exert dual, excitatory as well as inhibitory, post-junctional effects. Thus, the P2x-purinoceptor desensitizing agent, .alpha.,.beta.-methylene adenosine triphosphate, abolished the initial phase, but enhanced the amplitude of the neurogenic contraction, without affecting the nerve stimulation-induced overflow of [3H]noradrenaline. The results indicate that noradrenaline and adenosine triphosphate, the main mediators of the neurogenic contraction of this preparation, act in a more complex fashion than earlier thought; they argue against a significant direct contribution by other putative transmitters but do not exclude that such agents may act indirectly as modulators of this response.