Biol Reprod 2001; 64: 974–982.
Editorial comment: Erectile dysfunction associated with aging has been related to morphological changes occurring in the corpora cavernosa including loss of smooth muscle content and increased deposition of collagen. The functional correlate is believed to be altered compliance of the erectile tissue required for sustained penile erection. Insofar as the mechanisms associated with this pathology have remained open to investigation, this investigator group has sought to identify a possible pathogenic role for inducible nitric oxide synthase (iNOS). Their premise that iNOS is a determinant of age-related erectile dysfunction is built on the knowledge that this nitric oxide synthase (NOS) isoform is expressed to an increasingly greater extent with age in the rat brain and testis, with assumptions that this modification relates to tissue degeneration as a function of age. Distinct from the constitutive neuronal and endothelial NOS enzyme isoforms which release nitric oxide (NO) in fine amounts under tight physiological control, iNOS uniquely provides a source of the chemical that is released constantly and at comparatively greater levels into local tissues. The investigation consisted of a combined morphological and molecular analysis involving tissue image quantitation and markers of both iNOS expression and induction, tissue proteolysis and apoptosis in penile tissue from young (3–5-month-old) and old (24–30-month-old) rats. Markers of iNOS biology and most indicators of tissue degeneration were correlatively increased and corresponded with increase collagen deposition in old versus young tissues. These findings were contended by the investigators to indicate that an increased amount of NO is produced to counteract the higher rate of collagen deposition in the old penis, which thereby exerts a protective effect on erectile function. However, given the paradoxical role of NO in oversupply exerting deleterious effects as a cytotoxic agent, a possibility exists that the increased NO production and release may contribute to penile tissue derangement and fibrosis. While the expression of iNOS in age-related erectile dysfunction as shown in this study is quite intriguing, more investigation will definitely be needed to ascertain its actual role.
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