Erectile Dysfunction in Young Non-obese Type II Diabetic Goto-Kakizaki Rats is Associated with Decreased ENOS Phosphorylation at Ser1177

Overview

Journal J Sex Med

Publisher Oxford University Press

Specialties Gynecology & Obstetrics
Reproductive Medicine
Urology

Date 2010 Sep 3

PMID 20807325

Citations 14

Authors

Fernando S Carneiro

Fernanda R C Giachini

Zidonia N Carneiro

Victor V Lima

Adviye Ergul

R Clinton Webb

Rita C Tostes

Affiliations

Soon will be listed here.

Abstract

Introduction: Diabetes 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.

Aim: Goto-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.

Methods: Wistar 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 Measure: GK diabetic rats display ED associated with decreased cavernosal expression of eNOS protein.

Results: GK 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.

Conclusion: Although 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.

Citing Articles

EXPERIMENTAL INDUCTION OF TYPE 2 DIABETES MELLITUS AND THE EFFICIENCY OF BARIATRIC SURGERY IN ITS REVERSAL IN RATS.

Hritcu L, Borcea D, Anton E, Morosan S, Pasca S, Trinca C Acta Endocrinol (Buchar). 2021; 17(2):149-156.

PMID: 34925562 PMC: 8665240. DOI: 10.4183/aeb.2021.149.

Role of Glucose-Lowering Medications in Erectile Dysfunction.

Cignarelli A, Genchi V, DOria R, Giordano F, Caruso I, Perrini S J Clin Med. 2021; 10(11).

PMID: 34198786 PMC: 8201035. DOI: 10.3390/jcm10112501.

A novel experimental model of erectile dysfunction in rats with heart failure using volume overload.

Silva F, Veiga F, Mora A, Heck R, De Oliveira C, Gambero A PLoS One. 2017; 12(11):e0187083.

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Penile alterations at early stage of type 1 diabetes in rats.

Tao M, Tasdemir C, Tasdemir S, Shahabi A, Liu G Int Braz J Urol. 2017; 43(4):753-761.

PMID: 28338308 PMC: 5557453. DOI: 10.1590/S1677-5538.IBJU.2016.0454.

Constitutive NOS uncoupling and NADPH oxidase upregulation in the penis of type 2 diabetic men with erectile dysfunction.

Musicki B, Burnett A Andrology. 2017; 5(2):294-298.

PMID: 28076881 PMC: 5352463. DOI: 10.1111/andr.12313.

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