Nitric Oxide as a Mediator of Relaxation of the Corpus Cavernosum in Response to Nonadrenergic, Noncholinergic Neurotransmission

Lifestyle and metabolic approaches to maximizing erectile and vascular health

“…67 Response to PDE-5 inhibitors NO causes penile muscle relaxation by increasing cyclic GMP. 1 Consequently, all of the factors discussed above that increase NO would be expected to increase the response to PDE-5 inhibitors, which improve erectile function by inhibiting cyclic GMP breakdown and by enabling more frequent and sustained penile-specific exercise. PDE-5 inhibitors also can markedly improve antioxidant status.…”

“…It is remarkable that a compound as unstable as nitric oxide (NO) evolved as the critical factor determining the capacity for an erection, 1 and therefore perpetuation of our species. NO lasts only a few seconds in tissues due to its unbalanced electrons, and its production and stability depend on extensive antioxidant protection.…”

Nitric oxide and arthritis

“…Organic NO donors, such as nitroglycerin, have been used for decades to control angina and related cardio-vascular conditions. More recently, injection of these agents into the corpus cavernosum has been used as a successful, temporary treatment of impotence (86). Inhaled NO gas has been administered to patients with adult respiratory distress syndromes (87) and to neonates with persistent pulmonary hypertension.…”

Discovery of NO in the penis

“…It was not until January of 1992 that the NEJM article was finally published and the unique observation of this study, which set it apart from the other previously published rabbit and human data, was that PDE inhibition enhanced the NO-cGMP response of the corporal tissue (Figure 4). 3 It was only a few months later when Dr Burnett and his colleagues at Hopkins published their studies in the rat showing that not only was NO the mediator of penile erection in this animal model, but that NO was localized for the first time by antibody staining to the neurons in the penile tissue. 18 In early 1992, our group contacted Tom Lue in San Francisco to collaborate on a study that would use his dogs and our PDE inhibitor.…”

“…3 What actually caught the attention of the Pfizer scientists was the fact that phosphodiesterase inhibition actually enhanced the neurogenically induced vasorelaxation response of the corporal tissue since in an earlier unpublished Pfizer clinical study on angina, sildenafil appeared to possess some erectogenic side effects of an as yet unknown mechanism. Therefore, it was postulated that if their oral drug, sildenafil, possessed similar biochemical properties to the phosphodiesterase inhibitors used in the 1992 publication and did indeed enhance corporal smooth muscle relaxation, the compound could be a successful pro-erectogenic agent because it was becoming generally accepted at that time in the late 1980's that the major cause of erectile dysfunction in most men, regardless of age, was defective corporal smooth muscle relaxation or venous leakage which we now refer to as corporal veno-occlusive dysfunction.…”