Journal
INTERNATIONAL JOURNAL OF IMPOTENCE RESEARCH
Volume 15, Issue 1, Pages 53-62Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.ijir.3900947
Keywords
endothelin; endothelin receptor; Rho-kinase; corpus cavernosum smooth muscle; diabetes
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Funding
- NIDDK NIH HHS [DK55042, DK55529] Funding Source: Medline
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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.
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