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 II) were detected in high levels in rat urinary bladder. 3 Y-27632 (10 mM) signi®cantly attenuated contractions of rat urinary bladder strips evoked by the G-protein coupled receptor agonists carbachol (58.1+10.5% at 0.3 mM) and neurokinin A (68.6+12.7% at 1 mM) without a ecting contractions to potassium chloride (10 ± 100 mM). In addition, basal tone was reduced by 47.8+2.0% by 10 mM Y-27632 in the absence of stimulation. 4 Contractions of urinary bladder strips evoked by the P2X receptor agonist a,b-methylene ATP (a,b-mATP; 10 mM) were also attenuated by Y-27632 (30.0+7.2% at 10 mM). 5 Y-27632 (10 mM) signi®cantly attenuated contractions evoked by electrical ®eld stimulation (2 ± 16 Hz). The e ect of Y-27632 on the tonic portion of the neurogenic response (4 ± 16 Hz) was not signi®cantly di erent from the e ect of atropine (1 mM) alone. 6 While the mechanism underlying the ability of Y-27632 to inhibit a,b-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.
1 The e ects of L-NAME and zaprinast were investigated (i.v.) on re¯ex-evoked changes in bladder and urethral pressures in urethane-anaesthetized female rats. 2 L-NAME attenuated re¯ex-evoked urethral relaxations (65+10%), while zaprinast potentiated these responses (68+24%). L-NAME and zaprinast also increased baseline urethral pressure and urethral striated muscle (EUS-EMG) activity. These drugs had little e ect on the bladder. 3 Following pre-treatment with a-bungarotoxin (i.v.) to block urethral striated muscle, L-NAME and zaprinast failed to increase baseline urethral pressure. Further zaprinast failed to alter the size of re¯ex-evoked urethral relaxations. 4 Intra-urethral zaprinast caused a signi®cant increase while sodium nitroprusside (SNP) and isoprenaline caused decreases in urethral pressure (+14+3%, 725+5%, 729+7%, respectively). These changes were associated with increases in EUS-EMG activity. After chlorisondamine (i.v.), zaprinast caused a signi®cant fall in urethral pressure, while the decrease in urethral pressure caused by SNP and isoprenaline was potentiated. No changes in EUS-EMG activity occurred. 5 These results indicate that a nitrergic pathway mediates re¯ex-evoked urethral smooth muscle relaxations. The data also indicates that there is a background release of NO, which reduces sphincter skeletal muscle activity. Further, the ability of zaprinast to potentiate nitrergic evoked urethral relaxations involves an increase in striated muscle tone. This appears to be an indirect result of smooth muscle relaxation and is mediated, at least in part, by a chlorisondamine-sensitive mechanism.
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