title: Alterations of NOS, arginase, and DDAH protein expression in rabbit cavernous tissue after administration of cigarette smoke extract.
abstract: 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.
authors: Dept. of Biosystem Regulation, Tokyo Medical and Dental University, 2-3-10 Surugadai, Kanda, Chiyoda-ku, Tokyo 101-0062, Japan. mimamura.bsr@tmd.ac.jp
authors: Masatoshi
authors: M
authors: Imamura
authors: Yuma
authors: Y
authors: Waseda
authors: Galina Vasileva
authors: GV
authors: Marinova
authors: Tomoko
authors: T
authors: Ishibashi
authors: Satoshi
authors: S
authors: Obayashi
authors: Akihito
authors: A
authors: Sasaki
authors: Akiko
authors: A
authors: Nagai
authors: Hiroshi
authors: H
authors: Azuma
mesh_terms: D000581:Amidohydrolases / Q000096:biosynthesis*; D000818:Animals; D001119:Arginase / Q000096:biosynthesis*; D015153:Blotting, Western; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D010410:Penile Erection / Q000187:drug effects; D010413:Penis / Q000187:drug effects / Q000201:enzymology*; D011817:Rabbits; D012906:Smoke / Q000009:adverse effects / Q000032:analysis; D012907:Smoking / Q000378:metabolism*; D014026:Nicotiana / Q000737:chemistry
chemical_list: D007527:Isoenzymes; D012906:Smoke; D019001:Nitric Oxide Synthase; D000581:Amidohydrolases; D001119:Arginase; C059999:dimethylargininase; D006152:Cyclic GMP