| Research Abstract |
Recent studies have demonstrated that the Rho/Rho-kinase pathway plays an important role in various cellular functions, including actin cytoskeleton organization and vascular smooth muscle contraction. This pathway is also present in the central nervous system, and has been shown to be involved in the maintenance of dendritic spines, in the process of axon outgrowth, and in the regulation of neurotransmitter release. However, its role in central blood pressure regulation is totally unknown. The blockade of the Rho/Rho-kinase pathway in the nucleus tractus solitarii (NTS) of the brain stem by microinjection of a specific Rho-kinase inhibitor decreased blood pressure, heart rate, and renal sympathetic nerve activity in both Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). However, the magnitude of decreases in these variables was greater in SHR than in WKY. In addition, an adenovirus vector encoding dominant-negative Rho-kinase decreased blood pressure, heart rate, and urinary norepinephrine excretion in both WKY and SHR in the conscious state. The magnitude of decreases in these variables was also greater in SHR than in WKY. Furthermore, expression of RhoA in membrane and the activity of Rho-kinase in the NTS were enhanced in SHR as compared to WKY. These observations indicate that the Rho/Rho-kinase pathway in the NTS contributes to blood pressure regulation via the sympathetic nervous system in vivo, and that activation of this pathway may be involved in the central mechanisms of hypertension.
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