Erectile Dysfunction in Young Non-Obese Type II Diabetic Goto-Kakizaki Rats is Associated with Decreased eNOS Phosphorylation at Ser1177 |
| |
| Authors: | Fernando S Carneiro Fernanda RC Giachini Zidonia N Carneiro Victor V Lima Adviye Ergul R Clinton Webb Rita C Tostes |
| |
| Institution: | 2. Department of Pharmacology, University of Sao Paulo, Sao Paulo, SP, Brazil;3. Department of Pharmacology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, Brazil;1. Pacific Northwest National Laboratory, Richland, WA 99352, USA;2. Battelle Toxicology Northwest, Richland, WA 99352, USA;2. Institute of Cardiovascular Research, Pharma Research Centre, Bayer AG, Wuppertal, Germany;2. Department of Urology, China-Japan Union Hospital of Jilin University, Changchun, China;3. Department of Urology, School of Medicine, University of California, San Francisco, CA, USA;4. Department of Urology, General Hospital of Ningxia Medical University, Yinchuan, China;1. Department of Physiology, Augusta University, Augusta, GA, United States;2. Charlie Norwood Veterans Administration Medical Center, Augusta, GA, United States;1. Faculty of Rehabilitation Sciences, Nishikyushu University, 4490-9 Ozaki, Kanzaki, Saga, 842-8585, Japan;2. Center for Comprehensive and Community Medicine school of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849- 8501, Japan;3. Department of Anatomy and Physiology, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849- 8501, Japan |
| |
| Abstract: | IntroductionDiabetes mellitus (DM) is a risk factor for erectile dysfunction (ED). Although type 2 DM is responsible for 90–95% diabetes cases, type 1 DM experimental models are commonly used to study diabetes-associated ED.AimGoto-Kakizaki (GK) rat model is relevant to ED studies since the great majority of patients with type 2 diabetes display mild deficits in glucose-stimulated insulin secretion, insulin resistance, and hyperglycemia. We hypothesized that GK rats display ED which is associated with decreased nitric oxide (NO) bioavailability.MethodsWistar and GK rats were used at 10 and 18 weeks of age. Changes in the ratio of intracavernosal pressure/mean arterial pressure (ICP/MAP) after electrical stimulation of cavernosal nerve were determined in vivo. Cavernosal contractility was induced by electrical field stimulation (EFS) and phenylephrine (PE). In addition, nonadrenergic-noncholinergic (NANC)- and sodium nitroprusside (SNP)-induced relaxation were determined. Cavernosal neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) mRNA and protein expression were also measured.Main Outcome MeasureGK diabetic rats display ED associated with decreased cavernosal expression of eNOS protein.ResultsGK rats at 10 and 18 weeks demonstrated impaired erectile function represented by decreased ICP/MAP responses. Ten-week-old GK animals displayed increased PE responses and no changes in EFS-induced contraction. Conversely, contractile responses to EFS and PE were decreased in cavernosal tissue from GK rats at 18 weeks of age. Moreover, GK rats at 18 weeks of age displayed increased NANC-mediated relaxation, but not to SNP. In addition, ED was associated with decreased eNOS protein expression at both ages.ConclusionAlthough GK rats display ED, they exhibit changes in cavernosal reactivity that would facilitate erectile responses. These results are in contrast to those described in other experimental diabetes models. This may be due to compensatory mechanisms in cavernosal tissue to overcome restricted pre-penile arterial blood supply or impaired veno-occlusive mechanisms. Carneiro FS, Giachini FRC, Carneiro ZN, Lima VV, Ergul A, Webb RC, and Tostes RC. Erectile dysfunction in young non-obese type II diabetic Goto-Kakizaki rats is associated with decreased eNOS phosphorylation at Ser1177. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
