Conclusion

Emerging work supports a strong relationship between ED and oxidative stress. Basic science studies show that NADPH oxidase and/or eNOS uncoupling are sources of ROS in the penis in several vascular disease states associated with ED and priapism (see Fig. 28.3) and define several cellular targets of oxidative stress in the penis. However, the sources of ROS, the precise mechanisms of ROS production, the interaction between different ROS generating sources, the interaction between ROS-generating sources and endothelial NO/RhoA/ROCK pathways, and precise cellular targets for ROS in the penis, are still not well characterized in vas-culogenic ED. Furthermore, the status of the antioxidant systems that reduce ROS bioavailability in the diseased penis is controversial and needs further clarification.

ROS sources Antioxidants in the penis in the penis

ROS sources Antioxidants in the penis in the penis

Aging

eNOS uncoupling

-,î SOD | GSH/GSSG

Diabetes mellitus

NADPH oxidase eNOS uncoupling

-, | SOD i Catalase |,ÎGSH,-Gpx1

Hypertension

NADPH oxidase

i SOD

Hypercholesterolemia

NADPH oxidase eNOS uncoupling

Î SOD - Catalase -GPx

Cigarette smoking

NADPH oxidase

?

Hyperhomocysteinemia

?

?

Sickle cell disease

NADPH oxidase eNOS uncoupling

?

Fig. 28.3 Summary of the known ROS-generating sources and antioxidants in the penis in ED states. - Indicates no change; t indicates increase; I indicates decrease

Fig. 28.3 Summary of the known ROS-generating sources and antioxidants in the penis in ED states. - Indicates no change; t indicates increase; I indicates decrease

The molecular mechanisms of ROS production and their actions in nerves supplying the penis, which lead to neurogenic ED, are poorly defined to date. Continued research in the field should elucidate whether targeting ROS formation, rather than ROS removal, may be more effective as a therapeutic strategy to reduce oxidative damage in the penis and ED. More clinical studies designed to address the role of oxidative stress in ED are warranted to translate findings from basic science to clinical practice and to determine the clinical significance of decreasing oxidative stress in ED.

28.13 Key Points

• Increased oxidative stress has emerged as a major pathophysiologic mechanism underlying the development and progression of both vasculogenic and neuro-genic ED.

• NADPH oxidase is a source of ROS in the penis in ED associated with diabetes mellitus, hypertension, hypercholesterolemia, cigarette smoking, and SCD.

• eNOS uncoupling is a source of ROS in the penis in ED associated with aging, diabetes mellitus, hypercholesterolemia, and SCD.

• In vasculogenic ED, the main consequences of increased oxidative stress are decreased endothelial function (NO availability) and increased vasoconstriction.

• In neurogenic ED, the main consequences of increased oxidative stress are dysfunctional neurotransmission and apoptosis of nitrergic nerves.

• Basic science data suggest potential effect of antioxidants on improving erectile function in disease states. However, there is no evidence basis to support recommendations for using antioxidants or agents to reduce ROS production in the treatment of ED.

Pregnancy Guide

Pregnancy Guide

A Beginner's Guide to Healthy Pregnancy. If you suspect, or know, that you are pregnant, we ho pe you have already visited your doctor. Presuming that you have confirmed your suspicions and that this is your first child, or that you wish to take better care of yourself d uring pregnancy than you did during your other pregnancies; you have come to the right place.

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