Chonnam Med J.  2009 Apr;45(1):1-8. 10.4068/cmj.2009.45.1.1.

Oxidative Stress and Molecular Reactions in Arteriogenic Erectile Dysfunction

• Azadzoi KM
• Siroky M

• KMID: 2172277
• DOI: http://doi.org/10.4068/cmj.2009.45.1.1

Abstract

Vascular disorders are the leading causes of organic erectile dysfunction (ED). Most cases of arteriogenic ED are associated with vascular risk factors such as hypercholesterolemia, atherosclerosis, diabetes mellitus, hypertension, and smoking. These conditions impair vascular structure directly or indirectly by facilitating oxidative damage due to accumulation of reactive oxygen and nitrogen species such as superoxide (O2-), hydrogen peroxide (H2O2), hydroxyl radicals and peroxynitrite (O=NOO-). Clinical studies have shown that the degree of arteriogenic ED cannot be predicted exclusively by the arterial integrity, suggesting that it involves local changes within penile smooth muscle cells, endothelium, nerves, and microvasculature. It is thought that arterial occlusion and subsequent lack of erectile tissue perfusion, nutrient deficiency, hypoxia, and accumulation of waste products constitute an environment hospitable to free radical formation and detrimental to nitric oxide (NO) bioavailability. Studies of animal and cell culture models have revealed that exposure to ischemia and hypoxia triggers a cascade of cellular and molecular changes in the erectile tissue with devastating impact on its structure and function. These alterations involve cytotoxic radicals, nitric oxide synthase (NOS), eicosanoids, neurotoxic elements, and growth factors and lead to impairment of NO/cGMP pathway, smooth muscle dysfunction, microvascular damage, and neurodegeneration. Ultimately, these events lead to erectile tissue fibrosis and the failure of penile veno-occlusive mechanism. These local changes in the hypoxic erectile tissue may explain the failure of revascularization surgery to completely cure arteriogenic ED and imply the need for newer therapeutic strategies to remove cytotoxic and neurotoxic elements from the chronically ischemic penis.

Keyword

Atherosclerosis; Ischemia; Oxidative stress; Erectile dysfunction

MeSH Terms

Animals
Anoxia
Atherosclerosis
Biological Availability
Cell Culture Techniques
Diabetes Mellitus
Eicosanoids
Endothelium
Erectile Dysfunction
Fibrosis
Hydrogen Peroxide
Hypercholesterolemia
Hypertension
Intercellular Signaling Peptides and Proteins
Ischemia
Male
Microvessels
Muscle, Smooth
Myocytes, Smooth Muscle
Nitric Oxide
Nitric Oxide Synthase
Nitrogen
Oxidative Stress
Oxygen
Perfusion
Peroxynitrous Acid
Risk Factors
Smoke
Smoking
Superoxides
Waste Products
Eicosanoids
Hydrogen Peroxide
Intercellular Signaling Peptides and Proteins
Nitric Oxide
Nitric Oxide Synthase
Nitrogen
Oxygen
Peroxynitrous Acid
Smoke
Superoxides
Waste Products

Figure

• 

  Fig. 1 This figure shows the effects of ischemia on cavernosal VEGF, VEGF receptor (KDR), nNOS, and TGF-β gene expression. The ratio of the specific gene product and GAPDH is shown at each time point after the induction of cavernosal ischemia in the rabbit. VEGF levels show approximately a 2-fold increase compared with normal at 8 weeks of ischemia, with a reduction at 16 weeks. KDR levels decrease initially to half of normal and then gradually increase up to 8 weeks of ischemia. nNOS levels show a 2-fold increase at 6 weeks of ischemia and it decreases thereafter. TGFβ levels increase at 8 weeks of ischemia, but return to normal levels by 16 weeks. (From Wang et al, Int J Impot Res 16: 403-411, 2004).

• 

  Fig. 2 The left panel shows percentage of free radicals neutralized by several beverages known for their antioxidant capacity. The right panel shows antioxidant effect of pomegranate juice on macrophage (J-774. A1 cell line) oxidative status. Inhibition of cellular oxidative stress was measured by the DCFH fluorescence assay using the FACS system (From Azadzoi et al, J Urology 174: 386-93, 2005).

• 

  Fig. 3 This figure shows effects of the antioxidant beverage pomegranate juice (PJ) on erectile response to cavernosal nerve stimulation in the rabbit model. Long-term antioxidant consumption improved intracavernosal blood flow and erectile response in both arteriogenic ED and age-matched control animals. Arrows point to the start of electrical nerve stimulation (From Azadzoi et al, J Urology 174: 386-93, 2005).

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