blebbistain, a myosin ii inhibitor, as a novel strategy to regulate detrusor contractility in a rat model of partial bladder outlet obstructionblebbistain,肌球蛋白ii抑制剂,作为新策略来调节逼尿肌收缩在老鼠模型中部分膀胱出口梗阻.pdf

Blebbistain, a Myosin II Inhibitor, as a Novel Strategy to Regulate Detrusor Contractility in a Rat Model of Partial Bladder Outlet Obstruction 1,2 2 1,2 Xinhua Zhang , Allen Seftel , Michael E. DiSanto * 1 Department of Urology, Albert Einstein College of Medicine, Bronx, New York, United States of America, 2 Department of Surgery/Division of Urology, Cooper Medical School of Rowan University, Camden, New Jersey, United States of America Abstract Partial bladder outlet obstruction (PBOO), a common urologic pathology mostly caused by benign prostatic hyperplasia, can coexist in 40–45% of patients with overactive bladder (OAB) and is associated with detrusor overactivity (DO). PBOO that induces DO results in alteration in bladder myosin II type and isoform composition. Blebbistatin (BLEB) is a myosin II inhibitor we recently demonstrated potently relaxed normal detrusor smooth muscle (SM) and reports suggest varied BLEB efficacy for different SM myosin (SMM) isoforms and/or SMM vs nonmuscle myosin (NMM). We hypothesize BLEB inhibition of myosin II as a novel contraction protein targeted strategy to regulate DO. Using a surgically-induced male rat PBOO model, organ bath contractility, competitive and Real-Time-RT-PCR were performed. It was found that obstructed-bladder weight significantly increased 2.74-fold while in vitro contractility of detrusor to various stimuli was impaired ,50% along with decreased shortening velocity. Obstruction also altered detrusor spontaneous activities with significantly increased amplitude but depressed frequency. PBOO switched bladder from a phasic-type to a more tonic-type SM. Expression of 5’ myosin heavy chain (MHC) alternatively spliced isoform SM-A (associated with tonic-type SM) increased 3-fold while