Mechanisms of bradykinin-induced cerebral vasodilatation in rats: Evidence that reactive oxygen species activate K+ channels

Abstract

Background and Purpose: Relatively little is know regarding mechanisms by which reactive oxygen species produce dilatation of cerebral arterioles. The goal of this study was to test the hypothesis that vasodilator responses of cerebral arterioles to bradykinin, which produces endogenous generation of reactive oxygen species, involve activation of calcium-dependent potassium channels. Methods: We used a cranial window in anesthetized rats to examine effects of catalase (which degrades hydrogen peroxide) on responses to bradykinin. In addition, we examined effects of tetraethylammonium (TEA) and iberiotoxin, inhibitors of calcium-dependent potassium channels, on responses of cerebral arterioles to hydrogen peroxide, bradykinin, and papaverine. Results: In cerebral arterioles (baseline diameter=40±l μm) (mean±SE), hydrogen peroxide (10 and 100 μmol/L) produced concentration-dependent dilatation. TEA (1 mmol/L), an inhibitor of calcium-dependent potassium channels, produced marked inhibition of vasodilatation in response to hydrogen peroxide. For example, 100 μmol/L hydrogen peroxide dilated arterioles by 13±2% in the absence and 4±1% (P