Protease-activated receptor 2 and bradykinin-mediated vasodilation in the cerebral arteries of stroke-prone rats.

Protease-activated receptor 2 (PAR(2)) expression is up-regulated during vascular injury associated with edema. PAR(2) and bradykinin subtype 2 receptor (B(2)) expression and function were assessed in relation to hypertensive encephalopathy (HE) and cerebral hemorrhage (CH) in middle cerebral arteries (MCA) of Kyoto Wistar stroke-prone spontaneously hypertensive rats (SHRsp). Before stroke, bradykinin and PAR(2) activation by 2-furoyl-leucine-isoleucine-glycine-arginine-leucine-ornithine-amide (2Fly) produced endothelium-dependent vasodilation that was inhibited by K(+) depolarization, carbenoxolone, and the blockade of intermediate (IK(Ca)) plus small (SK(Ca)) and (in the case of bradykinin) smooth muscle (SM) large conductance (BK(Ca)) calcium-activated K(+) channels. Responses were not altered by N omega-nitro-L-arginine methyl ester, indomethacin, 17-octadecynoic acid or Ba(2+)+ouabain. We concluded that vasodilation to 2Fly or bradykinin was not mediated by NO, cyclooxygenases, arachidonic acid-metabolizing cytochrome P450s or SM K(ir) channels+Na(+)/K(+) ATPase activation. Vasodilation likely involved the spread of endothelial hyperpolarization (generated by IK(Ca)+SK(Ca)) through myoendothelial junctions and in some cases SM BK(Ca) activation. SHRsp with HE or CH had MCA that could not constrict to pressure and did not vasodilate to bradykinin. Their responses to 2Fly remained unaltered. The patterns and densities of PAR(2) and B(2) immunoreactivity in frozen MCA sections were not altered with stroke. MCA function remained normal in SHRsp subjected to dietary manipulations that prevented stroke without altering hypertension. Despite the presence of vascular injury, edema, inflammation and the loss of endothelium-dependent bradykinin vasodilation we found no evidence that PAR(2) expression or vascular function was altered in MCA after stroke.