An increment in a cytoplasmic Ca2+ concentration is the key event in smooth muscle contraction. However, smooth muscle contraction is modified upon the stimulation by agonists as well as in some pathophysiological situations through a Ca2+-independent mechanism. The molecular mechanism underlying this modulation has not been elucidated. Small GTPase Rho regulates cytoskeleton, cell adhesion, cell motility, and smooth muscle contraction through its specific effector proteins. Recent studies have shown the important role of Rho and its effector, Rho-associated kinase (Rho-kinase)/ROK/ROCK in Ca2+-independent regulation of smooth muscle contraction. The Rho/Rho-kinase pathway is involved in cardiovascular diseases such as hypertension and vasospasm, and it is a potent target of new therapies for not only cardiovascular diseases, but also for the protection of multiple organs.
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