Rho-kinase, a potential therapeutic target for the treatment of hypertension

Yoshitaka Hirooka, Hiroaki Shimokawa, Akira Takeshita

    Research output: Contribution to journalReview articlepeer-review

    26 Citations (Scopus)

    Abstract

    Hypertension is a cardiovascular disorder characterized by increased peripheral vascular resistance and/or vascular structural remodeling. Recently, rapidly growing evidence from hypertensive animal models suggests that small GTPase Rho and its downstream effector, Rho-kinase, play an important role in the pathogenesis of hypertension. Activation of the Rho/Rho-kinase pathway is essential for smooth muscle contractility in hypertension. A greater RhoA expression and an enhanced RhoA activity have been observed in aortas of hypertensive rats, such as genetic spontaneously hypertensive rats and N ω-nitro-L-arginine methyl ester-induced hypertension. The enhanced RhoA expression and activity was already observed in young spontaneously hypertensive rats before the onset of hypertension. These results suggest that both genetic factors and blood pressure can upregulate RhoA expression. Moreover, Y-27632 or fasudil, the specific Rho-kinase inhibitors, markedly decreased blood pressure in various hypertensive model rats, but did not in normotensive animals. In addition, Rho-kinase inhibitors have been shown to inhibit hypertensive vascular lesion formation. Therefore, Rho-kinase inhibitors may have a therapeutic potential for the treatment of hypertensive patients.

    Original languageEnglish
    Pages (from-to)523-527
    Number of pages5
    JournalDrug News and Perspectives
    Volume17
    Issue number8
    DOIs
    Publication statusPublished - Oct 2004

    All Science Journal Classification (ASJC) codes

    • Pharmacology
    • Drug Discovery

    Fingerprint Dive into the research topics of 'Rho-kinase, a potential therapeutic target for the treatment of hypertension'. Together they form a unique fingerprint.

    Cite this