Pharmacological analysis of vasoconstrictor responses to periarterial purinergic nerve stimulation.
1. Periarterial electrical nerve stimulation at a low frequency (1 Hz) readily induced a vasoconstrictor response of the canine splenic artery in a pulse number-related manner (1-30 pulses of trains). The vasoconstrictor response to trains of up to 10 pulses at 1 Hz of stimulation appeared to be monophasic, whereas it became clearly distinguished into two phases at a longer train of 30 pulses. 2. The monophasic vasoconstrictor responses to trains of 1, 3 or 10 pulses were not modified by an alpha1-adrenoceptor blocking agent, prazosin (0.1 microM), but were completely inhibited by the P2X receptor desensitization with alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-methylene ATP; 1 microM). The 1st phase of vasoconstriction induced by a train length of 30 pulses was not influenced by the treatment with prazosin, but was abolished by alpha,beta-methylene ATP. The 2nd phase response was markedly inhibited by prazosin, and the remaining response of this phase was blocked by alpha,beta-methylene ATP. 3. Rauwolscine (0.3 microM), an alpha2-adrenoceptor antagonist, enhanced the vasoconstrictor responses to trains of 1, 3 or 10 pulses. Particularly at 10 pulses of electrical stimulation, the vasoconstrictor responses were significantly potentiated. The blockade of neuronal uptake of noradrenaline with imipramine (1 microM) did not affect the vasoconstrictor responses to trains of 1, 3 or 10 pulses. 4. It is concluded that short pulse trains of stimulation at a low frequency may selectively activate a purinergic component of sympathetic cotransmission, and the prejunctional alpha2-adrenergic feedback mechanism may tonically participate into the modulation of ATP release. Imipramine-sensitive neuronal uptake mechanism may not play an important role in regulating vascular responses to periarterial purinergic nerve stimulation.
Yang
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Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Chiba
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D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000320:Adrenergic Fibers / Q000187:drug effects / Q000502:physiology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D005260:Female; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology; D013157:Splenic Artery / Q000187:drug effects / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D011224:Prazosin