CHARACTERIZATION OF VASCULAR POSTSYNAPTIC NEUROPEPTIDE-Y RECEPTOR FUNCTION AND REGULATION .1. NPY-INDUCED CONSTRICTION IN ISOLATED RAT FEMORAL-ARTERY RINGS IS MEDIATED BY BOTH Y1 AND Y2 RECEPTORS - EVIDENCE FROM BENEXTRAMINE PROTECTION STUDIES

Neuropeptide Y (NPY), a potent pressor agent and vasoconstrictor, is t hought to contribute to the sympathetically mediated postsynaptic regu lation of blood pressure primarily through activation of vascular Y1 r ather than Y2 NPY receptors. However, data are available that conflict with this conclusion. In this article, the relative roles of postsyna ptic Y, and Y2 receptors as mediators of direct NPY-induced isolated r at femoral artery ring vasoconstriction were evaluated through use of selective Y, and Y2 agonists, [Leu31, Pro34]NPY ([Leu, Pro]NPY) and NP Y13-36 [NPY(13-36)], respectively, and the NPY receptor antagonist ben extramine (BXT). NPY, [Leu, Pro]NPY and NPY(13-36) were equipotent as vasoconstrictors, and constriction induced by each peptide, but not by the calcium channel agonist BAY K 8644 (BAY), was almost completely b locked by 10 muM BXT, Each of the three peptides also induced self- an d cross-desensitization and protection from BXT blockade, except that [Leu, Pro]NPY neither desensitized nor protected NPY(13-36)-associated responses. NPY also failed to protect [Leu, Pro]NPY- and NPY(13-36)-e licited constriction, and NPY(13-36) failed to provide self-protection , from BXT blockade. However, in these instances, as opposed to the [L eu, Pro]N PY-NPY(13-36) cross-protection experiments, the occurrence o f protection was probably masked by the relatively large magnitude of desensitization concurrently induced by the protecting peptide. Taken together, the present findings suggest that NPY-induced rat femoral ar tery vasoconstriction is mediated by separate, BXT-sensitive, postsyna ptic Y, ([Leu, Pro]NPY-activated) and Y2 [NPY(13-36)-activated] recept ors.