Erectile dysfunction in young non-obese type II diabetic goto-kakizaki rats is associated with decreased eNOS phosphorylation at ser1177

Fernando S. Carneiro, Fernanda R.C. Giachini, Zidonia N. Carneiro, Victor V. Lima, Adviye Ergul, R. Clinton Webb, Rita C. Tostes

Research output: Contribution to journalArticle

27 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3620-3634
Number of pages15
JournalJournal of Sexual Medicine
Volume7
Issue number11
DOIs
StatePublished - Nov 2010

Fingerprint

Nitric Oxide Synthase Type III
Erectile Dysfunction
Phosphorylation
Electric Stimulation
Phenylephrine
Nitroprusside
Type 2 Diabetes Mellitus
Arterial Pressure
Theoretical Models
Pressure
Nitric Oxide Synthase Type I
Proteins
Type 1 Diabetes Mellitus
Hyperglycemia
Biological Availability
Insulin Resistance
Diabetes Mellitus
Nitric Oxide
Outcome Assessment (Health Care)
Insulin

Keywords

  • Corpus Cavernosum
  • Erectile Dysfunction
  • Goto-Kakizaki
  • Type 2 Diabetes Mellitus

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology
  • Urology

Cite this

Erectile dysfunction in young non-obese type II diabetic goto-kakizaki rats is associated with decreased eNOS phosphorylation at ser1177. / Carneiro, Fernando S.; Giachini, Fernanda R.C.; Carneiro, Zidonia N.; Lima, Victor V.; Ergul, Adviye; Webb, R. Clinton; Tostes, Rita C.

In: Journal of Sexual Medicine, Vol. 7, No. 11, 11.2010, p. 3620-3634.

Research output: Contribution to journalArticle

Carneiro, Fernando S. ; Giachini, Fernanda R.C. ; Carneiro, Zidonia N. ; Lima, Victor V. ; Ergul, Adviye ; Webb, R. Clinton ; Tostes, Rita C. / Erectile dysfunction in young non-obese type II diabetic goto-kakizaki rats is associated with decreased eNOS phosphorylation at ser1177. In: Journal of Sexual Medicine. 2010 ; Vol. 7, No. 11. pp. 3620-3634.
@article{885651778f3d4060a57545cc3e1f988e,
title = "Erectile dysfunction in young non-obese type II diabetic goto-kakizaki rats is associated with decreased eNOS phosphorylation at ser1177",
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.",
keywords = "Corpus Cavernosum, Erectile Dysfunction, Goto-Kakizaki, Type 2 Diabetes Mellitus",
author = "Carneiro, {Fernando S.} and Giachini, {Fernanda R.C.} and Carneiro, {Zidonia N.} and Lima, {Victor V.} and Adviye Ergul and Webb, {R. Clinton} and Tostes, {Rita C.}",
year = "2010",
month = "11",
doi = "10.1111/j.1743-6109.2010.02000.x",
language = "English (US)",
volume = "7",
pages = "3620--3634",
journal = "Journal of Sexual Medicine",
issn = "1743-6095",
publisher = "Wiley-Blackwell",
number = "11",

}

TY - JOUR

T1 - Erectile dysfunction in young non-obese type II diabetic goto-kakizaki rats is associated with decreased eNOS phosphorylation at ser1177

AU - Carneiro, Fernando S.

AU - Giachini, Fernanda R.C.

AU - Carneiro, Zidonia N.

AU - Lima, Victor V.

AU - Ergul, Adviye

AU - Webb, R. Clinton

AU - Tostes, Rita C.

PY - 2010/11

Y1 - 2010/11

N2 - 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.

AB - 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.

KW - Corpus Cavernosum

KW - Erectile Dysfunction

KW - Goto-Kakizaki

KW - Type 2 Diabetes Mellitus

UR - http://www.scopus.com/inward/record.url?scp=78049473688&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78049473688&partnerID=8YFLogxK

U2 - 10.1111/j.1743-6109.2010.02000.x

DO - 10.1111/j.1743-6109.2010.02000.x

M3 - Article

C2 - 20807325

AN - SCOPUS:78049473688

VL - 7

SP - 3620

EP - 3634

JO - Journal of Sexual Medicine

JF - Journal of Sexual Medicine

SN - 1743-6095

IS - 11

ER -