Cigarette smoking is an independent risk factor for vasculogenic erectile dysfunction (ED). Nitric oxide (NO) has been demonstrated to be the principal mediator of cavernous smooth muscle relaxation and penile erection. Therefore, we examined whether or not enzyme activities and factors involved in the NO generation pathway are affected in rabbit corpus cavernosum after administration of nicotine-and tar-free cigarette smoke extract (CSE). CSE was prepared by bubbling a stream of cigarette smoke into phosphate-buffered saline. CSE was injected subcutaneously into adult male rabbits once a day for 5 wk. In the CSE group, significantly decreased cyclic GMP production as a marker of NO generation was associated with attenuated overall nitric oxide synthase (NOS) activity, enhanced arginase activity, accumulation of endogenous NOS inhibitors such as monomethylarginine (MMA) and asymmetric dimethylarginine (ADMA), and decreased dimethylarginine dimethylaminohydrolase (DDAH) activity as an metabolizing enzyme of endogenous NOS inhibitors. Neuronal NOS (nNOS) and DDAH I protein expression were decreased without altering endothelial NOS expression, while arginase I expression was upregulated. These results suggest that impaired NO production would result from blunted NOS activity, which is possibly brought about by the downregulation of nNOS protein, accumulation of endogenous NOS inhibitors, and enhanced arginase activity together with upregulation of arginase I protein in cavernous tissue. The impaired DDAH activity due to decreased expression of DDAH I protein would result in an accumulation of endogenous NOS inhibitors with CSE. These alterations may be relevant to induction of the erectile dysfunction following CSE. erectile dysfunction; nitric oxide generation pathway; anti-asymmetric dimethylarginine antibody; immunohistochemistry; Western blot ACCORDING TO FELDMAN ET AL. (18) and McVary et al. (39), there are strong parallels and shared risks among smoking, coronary artery disease, atherosclerosis, and erectile dysfunction (ED). Clinical and basic science studies provide strong indirect evidence that smoking may affect penile erection by impairment of endothelium-dependent smooth muscle relaxation. Numerous studies have shown endothelial dysfunction in ED in smokers and experimental models. A recent review summarized some proposed mechanisms such as the way in which free radicals and aromatic compounds decrease the endothelial synthesis of nitric oxide (NO), causing impaired endotheliumdependent relaxation of arteries, which is the earliest clinical sign of endothelial dysfunction (45). NO has been demonstrated to be the principal mediator of cavernous smooth muscle relaxation and penile erection (4, 14, 24, 30, 46 -48). However, the precise mechanisms of impairment of NO production with cigarette smoking have not been fully elucidated.NO production, on one hand, depends on nitric oxide synthase (NOS) activity and NOS protein expression. There are reports describing that NOS activity was decreased in the human ...

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The DWI signal is derived from the motion of water molecules, which represents the physiologic characteristics of the tissue of interest. The emerging evidence highlights the utility of DWI for bladder cancer detection and characterization. DWI is a potentially useful tool to individualize treatment strategies.

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