Increased contractility of diabetic rabbit corpora smooth muscle in response to endothelin is mediated via Rho-kinase β

TY - JOUR

T1 - Increased contractility of diabetic rabbit corpora smooth muscle in response to endothelin is mediated via Rho-kinase β

AU - Chang, S.

AU - Hypolite, J. A.

AU - Changolkar, A.

AU - Wein, A. J.

AU - Chacko, S.

AU - DiSanto, M. E.

PY - 2003/2

Y1 - 2003/2

N2 - Corpus cavernosum smooth muscle (CCSM) from rabbits made diabetic for 6 months as a result of alloxan injection exhibited increased sensitivity (3 vs 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 KC1 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 ROKβ 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.

AB - Corpus cavernosum smooth muscle (CCSM) from rabbits made diabetic for 6 months as a result of alloxan injection exhibited increased sensitivity (3 vs 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 KC1 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 ROKβ 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.

UR - https://www.scopus.com/pages/publications/0037301102

UR - https://www.scopus.com/pages/publications/0037301102#tab=citedBy

U2 - 10.1038/sj.ijir.3900947

DO - 10.1038/sj.ijir.3900947

M3 - Article

C2 - 12605241

SN - 0955-9930

VL - 15

SP - 53

EP - 62

JO - International Journal of Impotence Research

JF - International Journal of Impotence Research

IS - 1

ER -