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| Increased contractility of diabetic rabbit corpora smooth muscle in response to endothelin is mediated via Rho-kinase beta |
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| Author(s): Chang S, Hypolite J, Changolkar A, Wein AJ, Chacko S, DiSanto ME |
| Source: INTERNATIONAL JOURNAL OF IMPOTENCE RESEARCH Volume: 15 Issue: 1 Pages: 53-62 Published: FEB 2003 |
| Times Cited: 48 References: 44 |
| Abstract: Corpus cavernosum smooth muscle (CCSM) from rabbits made diabetic for 6 months as a result of alloxan injection exhibited increased sensitivity (3vs 9 nM EC50) and generated 20-50% greater force to endothelin-1 (ET-1) compared to CCSM from normal rabbits. In contrast, the force produced by the CCSM in response to KCl and phenylephrine was not significantly altered in diabetic CCSM. The increased ET-1 sensitivity is associated with a two to three-fold upregulation of ET receptor A at both mRNA and protein levels in diabetic CCSM. ET-1-induced CCSM contraction is largely dependent upon Rho-kinase (ROK), since it is almost completely blocked by Y-27632 (a highly selective ROK inhibitor). Furthermore, expression of ROKbeta isoform is selectively upregulated in CCSM from diabetic rabbits. Thus, an increased CCSM tone, modulated by sensitization of the endothelin-mediated contractile pathway via ROK, may be a key component of the molecular mechanism of diabetes-induced erectile dysfunction. |
| Document Type: Article |
| Language: English |
| Reprint Address: DiSanto, ME (reprint author), Univ Penn, Div Urol, 3010 Ravdin Courtyard,3400 Spruce St, Philadelphia, PA 19104 USA |
Addresses:
1. Univ Penn, Div Urol, Philadelphia, PA 19104 USA
2. Univ Penn, Dept Pathobiol, Philadelphia, PA 19104 USA |
| Publisher: NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND |
| Subject Category: Urology & Nephrology |
| IDS Number: 654NP |
| ISSN: 0955-9930 |
| DOI: 10.1038/sj.ijir.3900947 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |