Neurogenic double‐peaked vasoconstriction of human gastroepiploic artery is mediated by both α1‐ and α2‐adrenoceptors

1 The contribution of postjunctional P2X receptors and subtypes of α-adrenoceptors to vasoconstrictor responses following periarterial electrical nerve stimulation (PNS, 30 s trains of pulses at a frequency of 2, 4 or 8 Hz) was investigated in human gastroepiploic arteries. 2 The vasoconstrictor response to PNS at a stimulation of 4 or 8 Hz was a two-peaked response, whereas at a frequency of 2 Hz it appeared only as a late peak. All vasoconstrictions evoked by PNS were abolished by phentolamine, a nonselective α-adrenoceptor inhibitor, but not by α,β-methylene ATP, a P2X receptor-desensitizing agent. 3 The early peak to PNS at 4 or 8 Hz was abolished by prazosin, an α1-adrenoceptor antagonist, while the late one still remained, although it was markedly inhibited. The responses remaining after prazosin were blocked by rauwolscine. The vasoconstrictor response to PNS at 2 Hz was not affected by prazosin (0.1 μM), but was abolished by rauwolscine (0.1 μM), an α2-adrenoceptor antagonist. 4 OPC-28326(10 μM), a newly developed vasodilator, which preferentially exerts its antagonistic actions on the α2B- and α2C-adrenoceptors, significantly reduced the noradrenaline-induced vasoconstriction in the absence or presence of prazosin. OPC-28326 had a greater inhibitory effect on the late peak evoked by PNS than the early one. The neurogenic responses remaining after OPC-28326 were abolished by prazosin. 5 The present results suggest that sympathetic vasoconstriction of the human gastroepiploic artery is mediated by both α1- and α2-adrenoceptors postjunctionally, but not by P2X receptors. The α2-adrenoceptors may be preferentially activated at a low frequency of stimulation, which induces a constriction more slowly than that by α1-adrenoceptors. The existence of α2-adrenoceptors may cause an enhancement of α1-adrenoceptor-induced responses. British Journal of Pharmacology (2005) 144, 737–742. doi:10.1038/sj.bjp.0705975