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ENDOCRINE AND DIABETES

Alterations of Glucose-Dependent and -Independent Bladder Smooth Muscle Contraction in Spontaneously Hypertensive and Hyperlipidemic Rat

Department of Pharmacology, School of Pharmaceutical Sciences (K.N., T.Y., T.H., K.H.), and Department of Pharmacology, School of Medicine (M.O., S.I., K.O.), Showa University, Tokyo, Japan; and Department of Pharmacology, School of Medicine, St. Mariannna University, Miyamae-ku Kawasaki, Kanagawa, Japan (T.K., S.K.)

Alteration of bladder contractility was examined in the spontaneously hypertensive and hyperlipidemic rat (SHHR; age, 9 months; systolic blood pressure, >150 mm Hg; plasma cholesterol, >150 mg/dl). Carbachol (CCh) induced time- and dose-dependent contractions in Sprague-Dawley (age-matched control) rats and SHHR; however, maximal levels differed significantly (13.3 ± 2.2 and 5.4 ± 1.9 µN/mm² following 10 µM CCh treatment, respectively; n = 5). This difference, which was maintained in calcium-replaced physiological salt solution (PSS), was suppressed by pretreatment with rho kinase inhibitor, 1 µM Y27632 [(R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide]; moreover, total activity of rho kinase was also reduced in SHHR bladder. Pretreatment of bladders under high-glucose (HG) conditions (22.2 mM glucose-contained PSS for 30 min) led to enhancement of CCh-induced contraction solely in control animals. Under HG conditions, both protein kinase C (PKC) activity and production of diacylglycerol (DG) derived from incorporated glucose declined in SHHR bladder; however, sustained elevation of plasma glucose level was not detected in SHHR. These results suggested that bladder contractility dysfunction in SHHR is attributable to alteration of rho kinase activity and the DG-PKC pathway. This dysfunction may occur prior to chronic hyperglycemia onset in progressive hypertension and hyperlipidemia.

Address correspondence to: Dr. Koji Nobe, Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. E-mail: kojinobe{at}pharm.showa-u.ac.jp

This article has been cited by other articles:

				K. Nobe, T. Yamazaki, N. Tsumita, T. Hashimoto, and K. Honda Glucose-Dependent Enhancement of Diabetic Bladder Contraction Is Associated with a Rho Kinase-Regulated Protein Kinase C Pathway J. Pharmacol. Exp. Ther., March 1, 2009; 328(3): 940 - 950. [Abstract] [Full Text] [PDF]