Role of endothelium on the effects of neuropeptide Y in mesenteric resistance arteries of spontaneously hypertensive and Wistar-Kyoto normotensive rats

The role of the endothelium in the effects of neuropeptide Y (NPY) and norepinephrine was investigated in mesenteric resistance arteries of the spontaneously hypertensive rat (SHR) and of the normotensive Wistar-Kyoto rat (WKY). Endothelium-dependent relaxation to acetylcholine (1 microM) was reduced in arteries of SHR compared with WKY. In the presence of the endothelium, the vessels of the two strains responded similarly to norepinephrine and NPY (100 nM) produced only a slight contraction. After removal of the endothelium, the response to norepinephrine was greater in WKY than in SHR. Furthermore, endothelium denudation enhanced markedly contraction elicited by NPY in WKY (up to 40% of the maximal effect of norepinephrine), but not in SHR. NPY potentiated the contractile response to low concentrations of norepinephrine (less than 300 nM) in both strains regardless whether the endothelium was intact or not. These results indicate that the contractile responses to NPY and to norepinephrine are inhibited by the endothelium in vessels of WKY, but not in those of the SHR. Furthermore, the potentiating effect of NPY occurs via an endothelium-independent mechanism in mesenteric arteries of both SHR and WKY. It is proposed that the differential responses between the two strains are related to abnormal function of the endothelium and to decreased responsiveness of smooth muscle cells in mesenteric resistance arteries of SHR compared to WKY.