Effects of a selective neuropeptide Y Y(1) receptor antagonist BIBP 3226 on double peaked vasoconstrictor responses to periarterial nerve stimulation in canine splenic arteries.
The periarterial electrical nerve stimulation (30 s trains of pulses at a frequency of 1, 4 or 10 Hz) induced a double peaked vasoconstriction consisting of an initial transient constriction (first peak) followed by a prolonged response (second peak) in the isolated, perfused canine splenic artery. At low frequencies (1 and 4 Hz), a neuropeptide Y (NPY) Y(1) receptor antagonist BIBP 3226 (0.1-1 microM) produced a dose-dependent inhibitory effect on the second peak, but did not modify the first peak. At a high frequency (10 Hz), 1 microM BIBP 3226 induced a slight, but significant inhibition on both the first and second peaked responses. At a low frequency (1 Hz), the first peak was not influenced by blockade of alpha(1)-adrenoceptors or NPY Y(1) receptors with prazosin (0.1 microM) or BIBP 3226 (1 microM), respectively, but abolished by P2X receptor desensitization with alpha,beta-methylene ATP (alphabeta-m ATP, 1 microM). At a high frequency (10 Hz), the first peak was mostly inhibited by alphabeta-m ATP and partially by prazosin and BIBP 3226. On the other hand, the second peak at a low frequency was largely decreased by BIBP 3226 and partially by prazosin and alphabeta-m ATP, whereas at a high frequency, it was largely attenuated by prazosin and partially by alphabeta-m ATP and BIBP 3226. The results suggest that at a low frequency, the firstly transient constriction of double peaked responses is mainly induced via an activation of P2X-receptors, whereas at a high frequency, it is mostly mediated by the P2X-receptors, and partially by alpha(1)-receptors and NPY Y(1)-receptors. The secondary prolonged vasoconstriction at frequencies used is predominantly mediated via both alpha(1)-receptor and NPY Y(1) receptor activations, and in part by P2X-receptors. Furthermore, an activation of NPY Y(1) receptors may play an important role in evoking the prolonged vasoconstrictor response to longer pulse trains of stimulation at a low frequency, whereas an alpha(1)-adrenoceptor activation exerts a main vasomotor effect for the prolonged response at a high frequency.
Yang
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Department of Pharmacology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
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D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004285:Dogs; D004347:Drug Interactions; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009417:Nerve Tissue / Q000187:drug effects / Q000502:physiology; D009478:Neuropeptide Y / Q000031:analogs & derivatives* / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*; D013157:Splenic Artery / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D014151:Anti-Anxiety Agents; C092926:BIBP 3226; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C062259:neuropeptide Y, Leu(31)-Pro(34)-; D000255:Adenosine Triphosphate; D001120:Arginine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D009638:Norepinephrine; D011224:Prazosin