Expression and functional role of Rho-kinase in rat urinary bladder smooth muscle

1 The involvement of Rho-kinase (ROCK) in the contractile mechanisms mediating smooth muscle contraction of the rat urinary bladder was investigated using expression studies and the ROCK inhibitor Y-27632. 2 Both isoforms of ROCK (ROCK I and ROCK 11) were detected in high levels in rat urinary bladder. 3 Y-27632 (10 muM) significantly attenuated contractions of rat urinary bladder strips evoked by the G-protein coupled receptor agonists carbachol (58.1 +/- 10.5% at 0.3 muM) and neurokinin A (68.6 +/- 12.7% at 1 muM) without affecting contractions to potassium chloride (10-100 mM). In addition, basal tone was reduced by 47.8 +/- 2.0% by 10 pm Y-27632 in the absence of stimulation. 4 Contractions of urinary bladder strips evoked by the P2X receptor agonist alpha,beta-methylene ATP (alpha,beta-mATP; 10 muM) were also attenuated by Y-27632 (30.0 +/- 7.2% at 10 mum). 5 Y-27632 (10 muM) significantly attenuated contractions evoked by electrical field stimulation (216 Hz). The effect of Y-27632 on the tonic portion of the neurogenic response (4-16 Hz) was not significantly different from the effect of atropine (I mum) alone. 6 While the mechanism underlying the ability of Y-27632 to inhibit alpha,beta-mATP-evoked contractions remains undetermined, the results of the present study clearly demonstrate a role for ROCK in the regulation of rat urinary bladder smooth muscle contraction and tone.