Neuropeptide Y sub(2) receptors are involved in enhanced neurogenic vasoconstriction in spontaneously hypertensive rats

The present study addressed the role of neuropeptide (NPY) Y sub(2) receptors in neurogenic contraction of mesenteric resistance arteries from female spontaneously hypertensive rats (SHR). Arteries were suspended in microvascular myographs, electrical field stimulation (EFS) was performed, and protein evaluated by Western blotting and immunohistochemistry. In vasopressin-activated endothelium-intact arteries, NPY and fragments with selectivity for Y sub(1) receptors, [Leu super(31),Pro super(34)]NPY, Y sub(2) receptors, NPY(13-36), and rat pancreatic polypeptide evoked more pronounced contractions in segments from SHR than in Wistar Kyoto (WKY) arteries, even in the presence of the Y sub(1) receptor antagonist, BIBP3226 (0.3 mu M, (R)-N(2)-(diphenacetyl)-N-[(4-hydroxyphenyl)methyl]D-arginineamide ). In the presence of prazosin and during vasopressin activation, EFS-evoked contractions were larger in arteries from SHR compared to WKY. EFS contractions were enhanced by the Y sub(2) receptor selective antagonist BIIE0246TF (0.5 mu M, (S)-N2-[[1-[2-[4-[(R,S)-5,11-dihydro-6(6h)-oxodibenz [b,e]azepin-11-y1]-1-piperazinyl]-2-oxoethyl] cyclo-pentyl-N-[2-[1,2-dihydro-3,5 (4H)-dioxo-1,2-diphenyl-3H-1,2,4-triazol-4-yl]ethyl]-argininamide) , reduced by BIBP3226, and abolished by the combination of BIBP3226 and BIIE0246TF. Immunoblotting showed NPY Y sub(1) and Y sub(2) receptor expression to be similar in arteries from WKY and SHR, although a specific Y sub(2) receptor band at 80 kDa was detected only in arteries from WKY. Immunoreaction for NPY was enhanced in arteries from SHR. In contrast to arteries from WKY, BIIE0246TF increased NPY immunoreactivity in EFS-stimulated arteries from SHR. The present results suggest that postjunctional neuropeptide Y sub(1) and Y sub(2) receptors contribute to neurogenic contraction of mesenteric small arteries. Moreover, both enhanced NPY content and altered neuropeptide Y sub(1) and Y sub(2) receptor activation apparently contribute to the enhanced neurogenic contraction of arteries from SHR.