Rho-kinase and effects of Rho-kinase inhibition on the lower urinary tract.
Altered smooth muscle cell contractility/tone contributes, at least in part, to the lower urinary tract symptoms (LUTS) seen in men with benign prostatic obstruction (BPO). Accordingly, many of the therapies to date have focused largely on blockade of individual membrane receptors to diminish smooth muscle contractility and provide symptomatic relief. This pharmacologic approach has been associated with variable results, limited efficacy, and untoward side effects. Such limited clinical success is not surprising given the plethora of neurotransmitters, neuromodulators, and hormones that are now known to modulate LUT smooth muscle cell tone. In the pursuit of improved treatment options, more recent investigations have focused attention on intracellular signal transduction events that represent convergence points for membrane receptor activation. In particular, calcium sensitization and the role of the Rho-kinase pathway has received much attention. In this report, we review the literature on the role of the Rho-kinase pathway in the modulation of LUT smooth muscle cell tone. In short, the available data support an important role for Rho-kinase in the physiologic and pathophysiologic regulation of LUT smooth muscle cell tone. Rho-kinase inhibitors thus appear to represent a potentially attractive therapeutic possibility for the treatment of LUTS.
Christ
George J
GJ
Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. gchrist@wfubmc.edu
Andersson
Karl-Erik
KE
D000818:Animals; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D011467:Prostate / Q000201:enzymology; D011470:Prostatic Hyperplasia / Q000150:complications; D001743:Urinary Bladder / Q000201:enzymology; D053202:Urinary Incontinence, Urge / Q000188:drug therapy* / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D004791:Enzyme Inhibitors; D054460:rho-Associated Kinases