PMID- 17975012 OWN - NLM STAT- MEDLINE DCOM- 20080219 LR - 20220410 IS - 1521-0103 (Electronic) IS - 0022-3565 (Linking) VI - 324 IP - 2 DP - 2008 Feb TI - Alterations of glucose-dependent and -independent bladder smooth muscle contraction in spontaneously hypertensive and hyperlipidemic rat. PG - 631-42 AB - 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 microN/mm(2) following 10 microM 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 microM 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. FAU - Nobe, Koji AU - Nobe K AD - Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. kojinobe@pharm.showa-u.ac.jp. FAU - Yamazaki, Taigi AU - Yamazaki T FAU - Kumai, Toshio AU - Kumai T FAU - Okazaki, Masako AU - Okazaki M FAU - Iwai, Shinichi AU - Iwai S FAU - Hashimoto, Terumasa AU - Hashimoto T FAU - Kobayashi, Shinichi AU - Kobayashi S FAU - Oguchi, Katsuji AU - Oguchi K FAU - Honda, Kazuo AU - Honda K LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20071101 PL - United States TA - J Pharmacol Exp Ther JT - The Journal of pharmacology and experimental therapeutics JID - 0376362 RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Glucose/*metabolism MH - Hyperlipidemias/*metabolism MH - Hypertension/*metabolism MH - In Vitro Techniques MH - Male MH - Muscle Contraction/*physiology MH - Muscle, Smooth/*metabolism MH - Rats MH - Rats, Inbred SHR MH - Rats, Sprague-Dawley MH - Urinary Bladder/*metabolism EDAT- 2007/11/03 09:00 MHDA- 2008/02/20 09:00 CRDT- 2007/11/03 09:00 PHST- 2007/11/03 09:00 [pubmed] PHST- 2008/02/20 09:00 [medline] PHST- 2007/11/03 09:00 [entrez] AID - jpet.107.131334 [pii] AID - 10.1124/jpet.107.131334 [doi] PST - ppublish SO - J Pharmacol Exp Ther. 2008 Feb;324(2):631-42. doi: 10.1124/jpet.107.131334. Epub 2007 Nov 1.