Hypercholesterolemia-induced erectile dysfunction: endothelial nitric oxide synthase (eNOS) uncoupling in the mouse penis by NAD(P)H oxidase.

The Journal of Sexual Medicine
Biljana MusickiArthur L Burnett

Abstract

Hypercholesterolemia induces erectile dysfunction (ED) mostly by increasing oxidative stress and impairing endothelial function in the penis, but the mechanisms regulating reactive oxygen species (ROS) production in the penis are not understood. We evaluated whether hypercholesterolemia activates nicotinamide adenine dinucleotide phosphate (NAD[P]H) oxidase in the penis, providing an initial source of ROS to induce endothelial nitric oxide synthase (eNOS) uncoupling and endothelial dysfunction resulting in ED. Low-density-lipoprotein receptor (LDLR)-null mice were fed Western diet for 4 weeks to induce early-stage hyperlipidemia. Wild type (WT) mice fed regular chow served as controls. Mice received NAD(P)H oxidase inhibitor apocynin (10 mM in drinking water) or vehicle. Erectile function was assessed in response to cavernous nerve electrical stimulation. Markers of endothelial function (phospho [P]-vasodilator-stimulated-protein [VASP]-Ser-239), oxidative stress (4-hydroxy-2-nonenal [HNE]), sources of ROS (eNOS uncoupling and NAD[P]H oxidase subunits p67(phox) , p47(phox) , and gp91(phox) ), P-eNOS-Ser-1177, and eNOS were measured by Western blot in penes. The main outcome measures are the molecular mechanisms of ROS generatio...Continue Reading

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Citations

Jan 19, 2012·International Urology and Nephrology·Mehmet İlker GokceÖnder Yaman
Feb 4, 2011·International Journal of Impotence Research·J M JohnsonB Musicki
Dec 3, 2013·Pharmacology, Biochemistry, and Behavior·K DecaluwéJ Van de Voorde
Nov 21, 2014·The Journal of Sexual Medicine·Rodrigo A Fraga-SilvaNikolaos Stergiopulos
Dec 3, 2014·The Journal of Sexual Medicine·Tao LiuXiang Fang
Sep 29, 2011·The Journal of Sexual Medicine·Kelly DecaluwéJohan Van de Voorde
May 3, 2012·The Journal of Sexual Medicine·Olav SchjørringUlf Simonsen
Feb 18, 2015·The Journal of Sexual Medicine·Bart PauwelsJohan Van de Voorde
Oct 24, 2012·The Journal of Sexual Medicine·Mingchao LiZhangqun Ye
May 25, 2012·The Journal of Sexual Medicine·Biljana MusickiArthur L Burnett
Apr 12, 2012·The Journal of Sexual Medicine·Masaki KimuraBridget F Koontz
Jan 10, 2012·The Journal of Sexual Medicine·Irwin GoldsteinDonna Schena
Mar 13, 2014·The Journal of Sexual Medicine·Rodrigo A Fraga-SilvaNikolaos Stergiopulos
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Sep 1, 2020·American Journal of Hypertension·Amanda Almeida de Oliveira, Kenia Pedrosa Nunes

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