Neuropeptide YY1 receptor mediated mesenteric vasoconstriction in the pig in vivo

The object of the present study was to investigate the effects of the sympathetic cotransmitter neuropeptide Y (NPY), and the closely related gut hormone peptide YY (PYY), on splanchnic blood how regulation in the anaesthetized pig in vivo. Systemic injections of NPY, PYY and the NPY Y-1 receptor agonist [Leu(31)Pro(34)]NPY (470 pmol kg(-1) each) evoked presser and mesenteric vasoconstrictor responses that were largely abolished by the selective NPY Y-1 receptor antagonist H 409/22 (60 nmol kg(-1) min(-1)). In contrast, the NPY Y-2 receptor agonist N-acetyl[Leu(28)Leu(31)]NPY(24-36) (1.1 nmol kg(-1)), a dose of which potently evoked splenic NPY Y-2 receptor mediated (not affected by H 409/22) vasoconstriction, did not evoke any mesenteric vascular response. Mesenteric vascular responses to angiotensin II (10 pmol kg(-1)), alpha,beta -methylene ATP(10 nmol kg(-1)) and the alpha (1)-adrenoceptor agonist phenylephrine (15 nmol kg(-1)), were not inhibited by H 409/22. It is concluded that NPY and PYY evokes porcine mesenteric vasoconstriction mediated by the NPY Y-1 receptor subtype, as demonstrated by selective and specific inhibition exerted by the NPY Y-1 receptor antagonist H 409/22, in vivo. (C) 2000 Elsevier Science B.V. All rights reserved.