Nitric oxide/redox-based signalling as a therapeutic target for penile disorders

Abstract

Oxidative and/or nitrosative stress is implicated in the pathogeneses of assorted penile disorders of clinical significance, notably erectile dysfunction, priapism and penile fibrosis. It is becoming increasingly recognised that the generation and activity of reactive oxygen and nitrogen species in the penis influence vascular homeostasis of this organ, with adverse effects exerted at cellular and molecular levels. Furthermore, these elements may interact with molecular signalling pathways operating in the penis, modulating their functional roles. This interaction in particular suggests that by accessing molecular targets associated with oxidative/nitrosative stress in the penis, new pharmacotherapeutic approaches may be developed to promote normal erectile ability and preserve erectile tissue health. This notion pertains to, but also extends beyond, interventions which predictably target components of the nitric oxide-based signal transduction pathway for the on-demand treatment of erectile dysfunction. The next line of pharmaceuticals for disorders of the penis, in general, may well spawn from an integrative understanding of the complex regulatory interactions influenced by, as well as influencing nitric oxide signalling in this organ.

Keywords::

• erectile dysfunction
• guanylate cyclase activator
• nitric oxide synthase (NOS)
• nitrosative stress
• oxidative stress
• penile fibrosis
• phosphodiesterase type 5 inhibitor
• priapism
• reactive nitrogen species (RNS)
• reactive oxygen species (ROS)
• signal transduction

Acknowledgements

This work is gratefully supported by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases Grants DK-02568 and DK-67223 (to AL Burnett), the National Kidney Foundation–Maryland Professional Development Award (to B Musicki) and the American Heart Association National Center Grant 0530007N (to L Jin).