Raised tone reveals purinergic-mediated responses to sympathetic nerve stimulation in the rat perfused mesenteric vascular bed

Abstract

Noradrenaline and ATP are sympathetic co-transmitters. In rat isolated mesenteric small arteries, activation of sympathetic nerves can produce a vasoconstrictor response mediated by ATP. In contrast, the rat perfused mesenteric bed displays vasoconstrictor responses that are blocked solely by α 1-adrenoceptor antagonists. This study assessed the effect of raising tone with a vasoconstrictor on purinergic and noradrenergic responses to sympathetic nerve stimulation in the rat perfused mesentery. Rat mesenteric vascular beds were perfused with physiological salt solution and responses to nerve stimulation, or P2X-receptor agonists, were determined under basal conditions and after raising tone with endothelin-1. The contribution of noradrenaline and ATP to sympathetic nerve-mediated responses was assessed using the α 1-adrenoceptor antagonist, prazosin and the P2X-receptor desensitizing agent, α,β-methyleneATP. The effect of endothelin-1 on excitatory junction potentials generated in response to nerve stimulation in isolated mesenteric arteries was also assessed. Under baseline conditions, responses to nerve stimulation were mediated solely by activation of α 1-adrenoceptors. After raising perfusion pressure with endothelin-1 or the thromboxane mimetic 9,11-dideoxy-11α,9α-epoxymethanoprostaglandin F 2α (U44619), sympathetic nerve-mediated responses were larger than under basal conditions and the response was partly sensitive to P2X-receptor desensitization. Responses to exogenous P2X-receptor agonists were enhanced after treatment with endothelin-1, while endothelin-1 decreased the amplitude of excitatory junction potentials. These results indicate that ATP acts as an important, functional, sympathetic neurotransmitter in the perfused mesentery under raised tone conditions, where the perfusion pressure is closer to that found in vivo. This effect is due to a postjunctional enhancement of purinergic function.