Effects of a selective neuropeptide Y Y1 receptor antagonist BIBP 3226 on double peaked vasoconstrictor responses to periarterial nerve stimulation in canine splenic arteries

摘要

class="enumerated" style="list-style-type:decimal">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) Y1 receptor antagonist BIBP 3226 (0.1–1 μM) produced a dose-dependent inhibitory effect on the second peak, but did not modify the first peak. At a high frequency (10 Hz), 1 μM 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 α1-adrenoceptors or NPY Y1 receptors with prazosin (0.1 μM) or BIBP 3226 (1 μM), respectively, but abolished by P2X receptor desensitization with α,β-methylene ATP (αβ-m ATP, 1 μM). At a high frequency (10 Hz), the first peak was mostly inhibited by αβ-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 αβ-m ATP, whereas at a high frequency, it was largely attenuated by prazosin and partially by αβ-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 α1-receptors and NPY Y1-receptors. The secondary prolonged vasoconstriction at frequencies used is predominantly mediated via both α1-receptor and NPY Y1 receptor activations, and in part by P2X-receptors. Furthermore, an activation of NPY Y1 receptors may play an important role in evoking the prolonged vasoconstrictor response to longer pulse trains of stimulation at a low frequency, whereas an α1-adrenoceptor activation exerts a main vasomotor effect for the prolonged response at a high frequency.