Neurogenic double-peaked vasoconstriction of human gastroepiploic artery is mediated by both alpha1- and alpha2-adrenoceptors

Abstract

1. The contribution of postjunctional P2X receptors and subtypes of alpha-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 alpha-adrenoceptor inhibitor, but not by alpha,beta-methylene ATP, a P2X receptor-desensitizing agent. 3. The early peak to PNS at 4 or 8 Hz was abolished by prazosin, an alpha1-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 microM), but was abolished by rauwolscine (0.1 microM), an alpha2-adrenoceptor antagonist. 4. OPC-28326 (10 microM), a newly developed vasodilator, which preferentially exerts its antagonistic actions on the alpha2B- and alpha2C-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 alpha1- and alpha2-adrenoceptors postjunctionally, but not by P2X receptors. The alpha2-adrenoceptors may be preferentially activated at a low frequency of stimulation, which induces a constriction more slowly than that by alpha1-adrenoceptors. The existence of alpha2-adrenoceptors may cause an enhancement of alpha1-adrenoceptor-induced responses.

Figure 1

Vasoconstrictor responses to PNS and the effects of prazosin and rauwolscine in a perfused human isolated gastroepiploic artery. The vasoconstriction was induced by 30 s trains of pulses at 10 V amplitude and 1 ms pulse duration, over a frequency range of 2, 4 and 8 Hz.

Figure 2

Effects of prazosin and rauwolscine on the vasoconstrictor responses to PNS at 2 Hz (a), 4 Hz (b) and 8 Hz (c) in human gastroepiploic arteries. Data are presented as mean±s.e.m. (n=6). ^**P<0.01 as compared with the control group. ^##P<0.01 as compared with the preceding group.

Figure 3

Effects of rauwolscine on the vasoconstrictor responses to PNS at 2 Hz (a), 4 Hz (b) and 8 Hz (c) in human gastroepiploic arteries. Data are presented as mean±s.e.m. (n=5). ^**P<0.01 as compared with the control group. ^##P<0.01 as compared with the preceding group.

Figure 4

Vasoconstrictor responses to PNS and the effects of OPC-28326 in an isolated, perfused human gastroepiploic artery. The vasoconstriction was induced by 30 s trains of pulses at 10 V amplitude and 1 ms pulse duration, over a frequency range of 2, 4 and 8 Hz.

Figure 5

Effects of OPC-28326 on the vasoconstrictor responses to PNS at 2 Hz (a), 4 Hz (b) and 8 Hz (c) in human gastroepiploic arteries. Data are presented as mean±s.e.m. (n=6). ^**P<0.01 as compared with the control group. ^##P<0.01 as compared with the preceding group.

Figure 6

Effects of OPC-28326 on the vasoconstrictor responses to exogenously administered NA in human gastroepiploic arteries. Data are presented as mean±s.e.m. (n=6). ^**P<0.01 as compared with the control group. ^##P<0.01 as compared with the OPC-28326 group.

Figure 7

Effects of OPC-28326 on the vasoconstrictor responses of human gastroepiploic arteries to exogenously administered NA in the presence of prazosin. Data are presented as mean±s.e.m. (n=6). ^**P<0.01 as compared with the control group. ^##P<0.01 as compared with the prazosin group.

Figure 8

Effects of OPC-28326 on the vasoconstrictor responses of human gastroepiploic arteries to exogenously administered phenylephrine. Data are presented as mean±s.e.m. (n=6). ^**P<0.01 as compared with the control group.