Enhanced Vascular Neuropeptide Y– Immunoreactive Innervation in Two Hypertensive Rat Strains

Abstract

Abstract Considerable evidence indicates an enhanced sympathetic innervation of resistance arterial smooth muscle in the spontaneously hypertensive rat (SHR) compared with its normotensive Wistar-Kyoto (WKY) control. In addition to sympathetic hyperinnervation, an increased vascular innervation by neuropeptide Y–containing fibers, which are known to exert a vasoconstrictive and trophic action in vascular smooth muscle, has also been described. In addition to genetic hypertension, the SHR expresses hyperactive behavior and hyperreactivity to stress. To determine whether the enhanced neuropeptide Y–immunoreactive vascular innervation is specifically associated with hypertension and/or these behavioral abnormalities, four genetically related, inbred rat strains were used: SHR, which are hypertensive and hyperactive; WKY rats, which are neither hypertensive nor hyperactive; WKHA, which are hyperactive but normotensive; and WKHT, which are hypertensive but not hyperactive. The present study demonstrated that whereas the hypertensive strains (SHR and WKHT) exhibited smooth muscle hypertrophy in both superior mesenteric and caudal arteries in adulthood (10 months) but not at a prehypertensive age (1 month), both arteries exhibited significantly increased neuropeptide Y–immunoreactive innervation at both ages. It was further observed that the mesenteric artery in WKHA, a normotensive strain, had significant smooth muscle hypertrophy at 10 months; however, neuropeptide Y innervation in this artery was no different from that of WKY controls. The findings indicate that there is a cosegregation of neuropeptide Y hyperinnervation of the vasculature with the hypertensive phenotype, evident as early as 1 month of life in the hypertensive strains, and this should be considered further as a contributory factor in genetic hypertension. Vascular smooth muscle hypertrophy, while evident in adult hypertensive rats, was also observed in the mesenteric artery (but not the caudal artery) of adult WKHA rats, suggesting that other factors besides genetic hypertension, possibly hyperreactivity to stress, are responsible for this specific hypertrophic change in WKHA rats.