The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
RhoA/Rho-kinase suppresses endothelial nitric oxide synthase in the penis: A mechanism for diabetes-associated erectile dysfunction
Open accessAbstract
Significant impairment in endothelial-derived nitric oxide is present in the diabetic corpus cavernosum. RhoA/Rho-kinase may suppress endothelial nitric oxide synthase (eNOS). Here, we tested the hypothesis that RhoA/Rho-kinase contributes to diabetes-related erectile dysfunction and down-regulation of eNOS in the streptozotocin (STZ)-diabetic rat penis. Colocalization of Rho-kinase and eNOS protein was present in the endothelium of the corpus cavernosum. RhoA/Rho-kinase protein abundance and MYPT-1 phosphorylation at Thr-696 were elevated in the STZ-diabetic rat penis. In addition, eNOS protein expression, cavernosal constitutive NOS activity, and cGMP levels were reduced in the STZ-diabetic penis. To assess the functional role of RhoA/Rho-kinase in the penis, we evaluated the effects of an adeno-associated virus encoding the dominant-negative RhoA mutant (AAVTCMV19NRhoA) on RhoA/Rho-kinase and eNOS and erectile function in vivo in the STZ-diabetic rat. STZ-diabetic rats transfected with AAVCMVT19NRhoA had a reduction in RhoA/Rho-kinase and MYPT-1 phosphorylation at a time when cavernosal eNOS protein, constitutive NOS activity, and cGMP levels were restored to levels found in the control rats. There was a significant decrease in erectile response to cavernosal nerve stimulation in the STZ-diabetic rat. AAVT19NRhoA gene transfer improved erectile responses in the STZ-diabetic rat to values similar to control. These data demonstrate a previously undescribed mechanism for the down-regulation of penile eNOS in diabetes mediated by activation of the RhoA/Rho-kinase pathway. Importantly, these data imply that inhibition of RhoA/Rho-kinase improves eNOS protein content and activity thus restoring erectile function in diabetes.
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Arginase: A Multifaceted Enzyme Important in Health and Disease
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Physiological role of ROCKs in the cardiovascular system
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Metadata
- Authors
- Bivalacqua, T. J., Champion, H. C., Usta, M. F., Cellek, S., Chitaley, K., Webb, R. C., Lewis, R. L., Mills, T. M., Hellstrom, W. J. G., & Kadowitz, P. J.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2004-06-07
- Volume
- 101
- Issue
- 24
- Pages
- 9121-9126
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2129938192
- Cited by
- 317
- References
- 31
- FWCI
- 13.32
- Type
- journal article
- Language
- en
- Open access
- green
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- Bivalacqua, T. J., Champion, H. C., Usta, M. F., Cellek, S., Chitaley, K., Webb, R. C., Lewis, R. L., Mills, T. M., Hellstrom, W. J. G., & Kadowitz, P. J. (2004). RhoA/Rho-kinase suppresses endothelial nitric oxide synthase in the penis: A mechanism for diabetes-associated erectile dysfunction. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0400520101
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