Role of Rho-kinase within the brain in abnormality of regulation of sympathetic nervous system in hypertension

最近的研究表明Rho/Rho激酶通路在多种细胞功能中起重要作用，包括肌动蛋白细胞骨架组织和血管平滑肌收缩。该途径也存在于中枢神经系统中，并且已显示参与树突棘的维持、轴突生长的过程以及神经递质释放的调节。然而，它在中枢血压调节中的作用是完全未知的。通过显微注射特异性Rho激酶抑制剂阻断脑干孤束核（NTS）中的Rho/Rho激酶通路，降低了Wistar-Kyoto大鼠（WKY）和自发性高血压大鼠（SHR）的血压、心率和肾交感神经活动。然而，这些变量的下降幅度在SHR中大于WKY。此外，腺病毒载体编码显性负性Rho激酶降低血压，心率，尿去甲肾上腺素排泄在WKY和SHR在清醒状态。这些变量的降低幅度也在SHR中大于WKY。此外，与WKY相比，SHR的NTS膜RhoA表达和Rho激酶活性均增强。这些观察结果表明，在NTS的Rho/Rho激酶通路有助于通过交感神经系统在体内的血压调节，并且该通路的激活可能参与高血压的中枢机制。

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.