Effects of local reduction in pressure on endothelium-dependent responses of cerebral arterioles.

Abstract

The goal of this study was to examine effects of local reductions in intravascular pressure and dP/dt on endothelium-dependent responses of cerebral arterioles in normotensive Wistar-Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). WKY and SHRSP underwent clipping of one carotid artery at 1 month of age. At 6 months of age, responses of pial arterioles were examined in vivo in anesthetized rats. Bilateral craniotomies were performed to expose pial arterioles in the sham-operated and clipped cerebral hemispheres. Pressure (servo-null) was measured in sham-operated and clipped pial arterioles, and arteriolar diameter was measured before and during suffusion with bradykinin, A23187, and nitroprusside. Carotid clipping normalized pial arteriolar pulse pressure but not mean pressure in SHRSP. Responses of sham-operated pial arterioles to bradykinin and A23187 were less in SHRSP than in WKY. Responses of sham-operated pial arterioles to nitroprusside were greater in SHRSP than in WKY. Carotid clipping in SHRSP normalized responses of pial arterioles to bradykinin but not A23187 and had no effect on responses to nitroprusside. These findings suggest that elevated intravascular pressure per se may contribute to impairment of endothelium-dependent relaxation to at least some agonists in cerebral arterioles during chronic hypertension. Furthermore, the findings lead us to speculate that arteriolar pulse pressure may play a more important role than mean pressure in development of impaired endothelium dilatation during chronic hypertension.