Neuropeptide Y-mediated constriction and dilation in rat middle cerebral arteries

Neuropeptide Y (NPY) is an important vasoconstrictor in the cerebral circul ation. Its constrictor response is because of activation of NPY receptors o n the vascular smooth muscle (VSM). Little is known regarding the effects o f NPY On the endothelium. In the current study, the authors tested the hypo thesis that NPY can either constrict or dilate rat middle cerebral arteries (MCAs). Constriction is elicited by stimulating receptors on the VSM; dila tion is elicited by stimulating receptors on the endothelium. Middle cerebr al arteries were isolated, cannulated with micropipettes, pressurized to 85 mm Hg, and luminally perfused. The extraluminal application of NPY (mixed agonist), [Leu(31), Pro(34)]-NPY (Y1 agonist), or NPY[13-36] (Y2 agonist) p roduced concentration-dependent constrictions. BIBP 3226 (Y] selective anta gonist) significantly attenuated the NPY- and [Leu(31), Pro(34)]-NPY-induce d constrictions. The luminal application of NPY, [Leu(31), Pro(34)]-NPY, an d NPY-[13-36] produced concentration-dependent dilations of MCAs. The maxim um dilation produced by the NPY receptor agonists was approximately 40% of the dilation elicited by the luminal administration of 10(-5) mol/L ATP. Di lations elicited by luminal NPY, [Leu(31), Pro(34)]-NPY, or NPY-[13-36] wer e abolished by inhibition of nitric oxide synthase with 10(-5) mol/L N-omeg a-nitro-L-arginine methyl ester (L-NAME) or removal of the endothelium. Dil ations produced by luminal NPY or luminal [Leu(31), Pro(34)]-NPY were not a ffected by BIBP 3226. Stimulation of NPY receptors on vascular smooth muscl e constricted MCAs. Stimulation of an NPY receptor other than the Y1 subtyp e on endothelium dilated the MCAs by releasing nitric oxide.