Alterations of NOS, arginase, and DDAH protein expression in rabbit cavernous tissue after administration of cigarette smoke extract.
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.
Imamura
Masatoshi
M
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
Waseda
Yuma
Y
Marinova
Galina Vasileva
GV
Ishibashi
Tomoko
T
Obayashi
Satoshi
S
Sasaki
Akihito
A
Nagai
Akiko
A
Azuma
Hiroshi
H
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
D007527:Isoenzymes; D012906:Smoke; D019001:Nitric Oxide Synthase; D000581:Amidohydrolases; D001119:Arginase; C059999:dimethylargininase; D006152:Cyclic GMP