The pleiotropic effects of inducible nitric oxide synthase (iNOS) on the physiology and pathology of penile erection.
The contribution of the neuronal and endothelial isoforms of nitric oxide synthase (nNOS and eNOS, respectively) in the synthesis of nitric oxide as a mediator of penile erection, at the levels of both the penile corpora cavernosa and the hypothalamic regions that control the erectile response, are well established. More recently, the role of the third NOS isoform, the inducible NOS (iNOS), has also started to be elucidated. iNOS does not appear to intervene directly in physiological penile erection or in its central control, but its transcriptional induction is postulated to be a key factor in two opposite related pathological processes, namely neurotoxicity in critical related regions of the hypothalamus during senescence, and as a defense mechanism against the aging or injury-associated fibrosis in the penile corpora cavernosa, the media of the penile arteries, and the tunica albuginea. By counteracting fibrosis that impairs cavernosal smooth muscle compliance, iNOS would protect the erectile tissue. However, further studies are needed to conclusively evaluate these putative roles in the two organs involved in reproductive function. In addition, whether iNOS induction during aging is a major cause in the net loss of trabecular smooth muscle in the corpora cavernosa through apoptosis, remains to be elucidated. The overall evaluation of these conflicting effects is important in order to decide whether pharmacological iNOS induction, or alternatively NO donors or L-arginine, may constitute a valid approach to prevent or treat penile fibrosis and vasculogenic erectile dysfunction.
Gonzalez-Cadavid
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NF
LABioMed at Harbor-UCLA Medical Center, Torrance, CA, and Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. ncadavid@ucla.edu.
Rajfer
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J
D000375:Aging / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis / Q000201:enzymology; D006801:Humans; D018783:Impotence, Vasculogenic / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D010410:Penile Erection; D010413:Penis / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D014158:Transcription, Genetic
D052247:Nitric Oxide Synthase Type II