Role of rho kinase in the functional and dysfunctional tonic smooth muscles.

Tonic smooth muscles play pivotal roles in the pathophysiology of debilitating diseases of the gastrointestinal and cardiovascular systems. Tonic smooth muscles differ from phasic smooth muscles in the ability to spontaneously develop myogenic tone. This ability has been primarily attributed to the local production of specific neurohumoral substances that can work in conjunction with calcium sensitization via signal transduction events associated with the Ras homolog gene family, member A (RhoA)/Rho-associated, coiled-coil containing protein kinase 2 (ROCK II) pathways. In this article, we discuss the molecular pathways involved in the myogenic properties of tonic smooth muscles, particularly the contribution of protein kinase C vs the RhoA/ROCK II pathway in the genesis of basal tone, pathophysiology and novel therapeutic approaches for certain gastrointestinal and cardiovascular diseases. Emerging evidence suggests that manipulation of RhoA/ROCK II activity through inhibitors or silencing of RNA interface techniques could represent a new therapeutic approach for various gastrointestinal and cardiovascular diseases.