Activation of protease-activated receptor 2 (PAR2) on vascular endothelial cells causes vasorelaxation. Nitric oxide (NO)-mediated vasorelaxation of the aorta is impaired in male SHRSP.Z-Lepr^fa/IzmDmcr (SP.ZF) rats with metabolic syndrome (MetS), but PAR2-mediated vasorelaxation is preserved. In the current study, we investigated whether PAR2-mediated vasorelaxation in the thoracic aorta and superior mesenteric artery (MA) differed by sex and arterial site in SP.ZF rats, and SHR.Cg-Lepr^cp/NDmcr (CP) rats at 23–26 weeks of age, two different models of MetS.
Vasorelaxation was examined using the organ bath method. In isolated aortas from SP.ZF rats, vasorelaxations evoked by 2fLIGRLO, a PAR2 agonist, and by acetylcholine (ACh) were greater in females than in males, but in the case of CP rats, only ACh-induced relaxation was greater in females. In MA, 2fLIGRLO-induced vasorelaxation was smaller in females than in males in both strains. However, ACh-induced relaxations did not differ between sexes. Nitroprusside-induced relaxation did not differ significantly between sexes or arterial sites.
The findings demonstrate the presence of sex- and arterial site-dependent differences in PAR2-mediated vasorelaxations in MetS. The results indicate less PAR2-mediated relaxation in MAs of female rats under the condition of a presumably maintained NO-mediated vasorelaxation pathway. Further studies are needed to elucidate the pathophysiological significance of lower capacity for vasorelaxation via PAR2 in females with MetS.