Role of Peroxisome Proliferator-Activated Receptor-{gamma} in Vascular Muscle in the Cerebral Circulation [Cerebral Circulation]

We examined the hypothesis that selective interference with PPAR in vascular muscle would impair NO-dependent responses and augment vasoconstrictor responses in the cerebral circulation. We studied mice expressing a dominant negative mutation in human PPAR (P467L) under the control of the smooth muscle myosin heavy chain promoter (S-P467L). In S-P467L mice, dilator responses to exogenously applied or endogenously produced NO were greatly impaired in cerebral arteries in vitro and in small cerebral arterioles in vivo. Select NO-independent responses, including vasodilation to low concentrations of potassium, were also impaired in S-P467L mice. In contrast, increased expression of wild-type PPAR in smooth muscle had little effect on vasomotor responses. Mechanisms underlying impairment of both NO-dependent and NO-independent vasodilator responses after interference with PPAR involved Rho kinase with no apparent contribution by oxidative stress–related mechanisms. These findings support the concept that via effects on Rho kinase–dependent signaling, PPAR in vascular muscle is a major determinant of vascular tone in resistance vessels and, in particular, NO-mediated signaling in cerebral arteries and brain microvessels. Considering the importance of NO and Rho kinase, these findings have implications for regulation of cerebral blood flow and the pathogenesis of large and small vessel disease in brain.

Source: Hypertension - October 8, 2014 Category: Cardiology Authors: De Silva, T. M., Modrick, M. L., Ketsawatsomkron, P., Lynch, C., Chu, Y., Pelham, C. J., Sigmund, C. D., Faraci, F. M. Tags: Cerebrovascular disease/stroke, Brain Circulation and Metabolism, Endothelium/vascular type/nitric oxide Cerebral Circulation Source Type: research