NADPH oxidase activation: A mechanism of hypertension-associated erectile dysfunction

Liming Jin, Gwen Lagoda, Romulo Leite, R. Clinton Webb, Arthur L. Burnett

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Introduction. Hypertension is a risk factor for erectile dysfunction (ED). The pathophysiologic basis of ED in hypertension remains largely unknown. Aim. The goal of this study was to test the hypothesis that increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity contributes to the development of hypertension-associated ED. Methods. Male Sprague-Dawley rats were implanted with osmotic pumps containing saline or angiotensin II (Ang II, 70 ng/min) for 28 days and treated with or without the NADPH oxidase inhibitor apocynin (10mM) in the drinking water. Main Outcome Measures. Erectile function was examined by measuring the mean arterial blood pressure (MAP) and intracavernosal pressure (ICP) upon electrical stimulation of the cavernous nerve. Protein expression levels of NADPH oxidase subunits were analyzed by Western blot. Reactive oxygen species production was determined by dihydroethidium (DHE) staining and thiobarbituric acid reactive substances (TBARS) assay. Results. Maximum ICP (MaxICP) and ICP area under the curve, which were normalized by MAP, were significantly reduced in Ang II-infused hypertensive rats compared to that of normotensive rats (P < 0.05). Protein expression of NADPH oxidase subunit p47 phox was significantly increased by 30% in Ang II-infused hypertensive rat penes along with increased DHE staining and TBARS levels (P < 0.05) when compared to that of controls. There were no significant changes in p67 phox or gp91 phox protein expression. Apocynin reduced NADPH oxidase protein expression and TBARS levels as well as improved MaxICP and ICP area under curve in Ang II-infused hypertensive rats (P < 0.05). Conclusions. These data suggest that activation of NADPH oxidase is a molecular mechanism for hypertension-associated ED. Apocynin treatment exerted protective effects on erectile function through inhibition of NADPH oxidase activity, thereby reducing oxidative stress in Ang II-infused hypertensive rats. This is the first study to identify the importance of NADPH oxidase in the regulation of erectile function in vivo.

Original languageEnglish (US)
Pages (from-to)544-551
Number of pages8
JournalJournal of Sexual Medicine
Volume5
Issue number3
DOIs
StatePublished - Mar 2008

Fingerprint

Erectile Dysfunction
NADP
Oxidoreductases
Hypertension
Thiobarbituric Acid Reactive Substances
Arterial Pressure
Pressure
Area Under Curve
Proteins
Staining and Labeling
Substance P
Angiotensin II
Drinking Water
Electric Stimulation
Sprague Dawley Rats
Reactive Oxygen Species
Oxidative Stress
Western Blotting
Outcome Assessment (Health Care)
acetovanillone

Keywords

  • Angiotensin
  • Apocynin
  • Erectile function
  • Penis
  • Reactive oxygen species
  • Superoxide

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology
  • Urology

Cite this

NADPH oxidase activation : A mechanism of hypertension-associated erectile dysfunction. / Jin, Liming; Lagoda, Gwen; Leite, Romulo; Webb, R. Clinton; Burnett, Arthur L.

In: Journal of Sexual Medicine, Vol. 5, No. 3, 03.2008, p. 544-551.

Research output: Contribution to journalArticle

Jin, Liming ; Lagoda, Gwen ; Leite, Romulo ; Webb, R. Clinton ; Burnett, Arthur L. / NADPH oxidase activation : A mechanism of hypertension-associated erectile dysfunction. In: Journal of Sexual Medicine. 2008 ; Vol. 5, No. 3. pp. 544-551.
@article{a97cb83fe4f941c8930253a7bc6fb886,
title = "NADPH oxidase activation: A mechanism of hypertension-associated erectile dysfunction",
abstract = "Introduction. Hypertension is a risk factor for erectile dysfunction (ED). The pathophysiologic basis of ED in hypertension remains largely unknown. Aim. The goal of this study was to test the hypothesis that increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity contributes to the development of hypertension-associated ED. Methods. Male Sprague-Dawley rats were implanted with osmotic pumps containing saline or angiotensin II (Ang II, 70 ng/min) for 28 days and treated with or without the NADPH oxidase inhibitor apocynin (10mM) in the drinking water. Main Outcome Measures. Erectile function was examined by measuring the mean arterial blood pressure (MAP) and intracavernosal pressure (ICP) upon electrical stimulation of the cavernous nerve. Protein expression levels of NADPH oxidase subunits were analyzed by Western blot. Reactive oxygen species production was determined by dihydroethidium (DHE) staining and thiobarbituric acid reactive substances (TBARS) assay. Results. Maximum ICP (MaxICP) and ICP area under the curve, which were normalized by MAP, were significantly reduced in Ang II-infused hypertensive rats compared to that of normotensive rats (P < 0.05). Protein expression of NADPH oxidase subunit p47 phox was significantly increased by 30{\%} in Ang II-infused hypertensive rat penes along with increased DHE staining and TBARS levels (P < 0.05) when compared to that of controls. There were no significant changes in p67 phox or gp91 phox protein expression. Apocynin reduced NADPH oxidase protein expression and TBARS levels as well as improved MaxICP and ICP area under curve in Ang II-infused hypertensive rats (P < 0.05). Conclusions. These data suggest that activation of NADPH oxidase is a molecular mechanism for hypertension-associated ED. Apocynin treatment exerted protective effects on erectile function through inhibition of NADPH oxidase activity, thereby reducing oxidative stress in Ang II-infused hypertensive rats. This is the first study to identify the importance of NADPH oxidase in the regulation of erectile function in vivo.",
keywords = "Angiotensin, Apocynin, Erectile function, Penis, Reactive oxygen species, Superoxide",
author = "Liming Jin and Gwen Lagoda and Romulo Leite and Webb, {R. Clinton} and Burnett, {Arthur L.}",
year = "2008",
month = "3",
doi = "10.1111/j.1743-6109.2007.00733.x",
language = "English (US)",
volume = "5",
pages = "544--551",
journal = "Journal of Sexual Medicine",
issn = "1743-6095",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - NADPH oxidase activation

T2 - A mechanism of hypertension-associated erectile dysfunction

AU - Jin, Liming

AU - Lagoda, Gwen

AU - Leite, Romulo

AU - Webb, R. Clinton

AU - Burnett, Arthur L.

PY - 2008/3

Y1 - 2008/3

N2 - Introduction. Hypertension is a risk factor for erectile dysfunction (ED). The pathophysiologic basis of ED in hypertension remains largely unknown. Aim. The goal of this study was to test the hypothesis that increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity contributes to the development of hypertension-associated ED. Methods. Male Sprague-Dawley rats were implanted with osmotic pumps containing saline or angiotensin II (Ang II, 70 ng/min) for 28 days and treated with or without the NADPH oxidase inhibitor apocynin (10mM) in the drinking water. Main Outcome Measures. Erectile function was examined by measuring the mean arterial blood pressure (MAP) and intracavernosal pressure (ICP) upon electrical stimulation of the cavernous nerve. Protein expression levels of NADPH oxidase subunits were analyzed by Western blot. Reactive oxygen species production was determined by dihydroethidium (DHE) staining and thiobarbituric acid reactive substances (TBARS) assay. Results. Maximum ICP (MaxICP) and ICP area under the curve, which were normalized by MAP, were significantly reduced in Ang II-infused hypertensive rats compared to that of normotensive rats (P < 0.05). Protein expression of NADPH oxidase subunit p47 phox was significantly increased by 30% in Ang II-infused hypertensive rat penes along with increased DHE staining and TBARS levels (P < 0.05) when compared to that of controls. There were no significant changes in p67 phox or gp91 phox protein expression. Apocynin reduced NADPH oxidase protein expression and TBARS levels as well as improved MaxICP and ICP area under curve in Ang II-infused hypertensive rats (P < 0.05). Conclusions. These data suggest that activation of NADPH oxidase is a molecular mechanism for hypertension-associated ED. Apocynin treatment exerted protective effects on erectile function through inhibition of NADPH oxidase activity, thereby reducing oxidative stress in Ang II-infused hypertensive rats. This is the first study to identify the importance of NADPH oxidase in the regulation of erectile function in vivo.

AB - Introduction. Hypertension is a risk factor for erectile dysfunction (ED). The pathophysiologic basis of ED in hypertension remains largely unknown. Aim. The goal of this study was to test the hypothesis that increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity contributes to the development of hypertension-associated ED. Methods. Male Sprague-Dawley rats were implanted with osmotic pumps containing saline or angiotensin II (Ang II, 70 ng/min) for 28 days and treated with or without the NADPH oxidase inhibitor apocynin (10mM) in the drinking water. Main Outcome Measures. Erectile function was examined by measuring the mean arterial blood pressure (MAP) and intracavernosal pressure (ICP) upon electrical stimulation of the cavernous nerve. Protein expression levels of NADPH oxidase subunits were analyzed by Western blot. Reactive oxygen species production was determined by dihydroethidium (DHE) staining and thiobarbituric acid reactive substances (TBARS) assay. Results. Maximum ICP (MaxICP) and ICP area under the curve, which were normalized by MAP, were significantly reduced in Ang II-infused hypertensive rats compared to that of normotensive rats (P < 0.05). Protein expression of NADPH oxidase subunit p47 phox was significantly increased by 30% in Ang II-infused hypertensive rat penes along with increased DHE staining and TBARS levels (P < 0.05) when compared to that of controls. There were no significant changes in p67 phox or gp91 phox protein expression. Apocynin reduced NADPH oxidase protein expression and TBARS levels as well as improved MaxICP and ICP area under curve in Ang II-infused hypertensive rats (P < 0.05). Conclusions. These data suggest that activation of NADPH oxidase is a molecular mechanism for hypertension-associated ED. Apocynin treatment exerted protective effects on erectile function through inhibition of NADPH oxidase activity, thereby reducing oxidative stress in Ang II-infused hypertensive rats. This is the first study to identify the importance of NADPH oxidase in the regulation of erectile function in vivo.

KW - Angiotensin

KW - Apocynin

KW - Erectile function

KW - Penis

KW - Reactive oxygen species

KW - Superoxide

UR - http://www.scopus.com/inward/record.url?scp=40349113071&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=40349113071&partnerID=8YFLogxK

U2 - 10.1111/j.1743-6109.2007.00733.x

DO - 10.1111/j.1743-6109.2007.00733.x

M3 - Article

C2 - 18208505

AN - SCOPUS:40349113071

VL - 5

SP - 544

EP - 551

JO - Journal of Sexual Medicine

JF - Journal of Sexual Medicine

SN - 1743-6095

IS - 3

ER -