Dietary antioxidants improve arteriogenic erectile dysfunction.
Most cases of erectile dysfunction (ED) are associated with oxidative stress risk factors such as diabetes mellitus, smoking, hypercholesterolaemia and hypertension. Our goal was to search for markers of oxidative stress in arteriogenic ED and examine the protective role of dietary antioxidants. Atherosclerosis-induced ED was developed in rabbits by balloon de-endothelialization of the iliac arteries. Ballooned and age-matched control animals were assigned into subgroups receiving pomegranate extract antioxidants in drinking water or tap water as placebo. After 8 weeks, penile blood flow and erectile activity were recorded. Erectile tissue relaxation, oxidative products, oxidative stress-responsive genes and structure were examined using organ bath, enzyme immunoassay, quantitative real-time polymerase chain reaction and transmission electron microscopy, respectively. Arterial ballooning caused diffused atherosclerosis, decreased intracavernosal blood flow and led to ED. Impairment of endothelium-dependent relaxation, diffused fibrosis, increased oxidative products, upregulation of superoxide dismutase (SOD) and aldose reductase (AR) gene expression, mitochondrial and endothelial structural damage and increased caveolae were evident in erectile tissues from atherosclerotic animals receiving placebo. Upregulation of antioxidant enzymes SOD and AR failed to protect ischaemic erectile tissue from oxidative injury. Pomegranate extract significantly improved intracavernosal blood flow, erectile activity, smooth muscle relaxation and fibrosis of the atherosclerotic group in comparison with the atherosclerotic group receiving placebo, but did not normalize them to the age-matched control levels. Pomegranate extract appeared more effective in diminishing oxidative products, preventing SOD and AR gene upregulation, and protecting mitochondrial, endothelial and caveolae structural integrity of the atherosclerotic group. Our data suggest the presence of oxidative stress in ED and a more efficient action of antioxidants on molecular and ultrastructural alterations than on distinct functional deficit and structural damage in the ischaemic penis.
Zhang
Q
Q
Department of Urology, VA Boston Healthcare System and Boston University School of Medicine, Boston, MA, USA.
Radisavljevic
Z M
ZM
Siroky
M B
MB
Azadzoi
K M
KM
D000449:Aldehyde Reductase / Q000235:genetics; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000209:etiology; D001783:Blood Flow Velocity; D004435:Eating; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000187:drug effects; D018783:Impotence, Vasculogenic / Q000150:complications / Q000178:diet therapy / Q000503:physiopathology; D007511:Ischemia / Q000150:complications; D029561:Lythraceae; D008297:Male; D046529:Microscopy, Electron, Transmission; D018384:Oxidative Stress; D010413:Penis / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D010936:Plant Extracts / Q000008:administration & dosage / Q000627:therapeutic use*; D011817:Rabbits; D013482:Superoxide Dismutase / Q000235:genetics
D000975:Antioxidants; D010936:Plant Extracts; D000449:Aldehyde Reductase; D013482:Superoxide Dismutase