Neurogenic double-peaked vasoconstriction of human gastroepiploic artery is mediated by both alpha1- and alpha2-adrenoceptors.
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.
Fukui
Daisuke
D
Department of Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan.
Yang
Xiao-Ping
XP
Chiba
Shigetoshi
S
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000368:Aged; D000814:Aniline Compounds / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D005260:Female; D024405:Gastroepiploic Artery / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D010880:Piperidines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000814:Aniline Compounds; D010880:Piperidines; D011942:Receptors, Adrenergic, alpha; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D015016:Yohimbine; C400276:OPC 28326; D009638:Norepinephrine; D011224:Prazosin