文章基本信息

标题：Effects of Nitric Oxide Synthase and Heme Oxygenase Inducers and Inhibitors on Molecular Signaling of Erectile Function
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作者：Mohammed Talaat Abdel Aziz ; Mohammed Farid El-Asmar ; Taymour Mostafa 等
期刊名称：Journal of Clinical Biochemistry and Nutrition
印刷版ISSN：0912-0009
电子版ISSN：1880-5086
出版年度：2005
卷号：37
期号：3
页码：103-111
DOI：10.3164/jcbn.37.103
出版社：The Society for Free Radical Research Japan
摘要：Changes in gene expression and the enzymatic activity of inducible nitric oxide synthase (iNOS), heme oxygenase isoenzymes 1 and 2 (HO-1 and HO-2) and cyclic GMP (cGMP) tissue levels in the corpora cavernosa (CC) were investigated experimentally in sixty Sprague-Dawley rats subjected to either HO or NOS inducers or inhibitors. They were divided into 5 groups ( n = 12/group): Control group, L-arginine group which received L-arginine as NOS inducer, L-nitroarginine methyl ester (L-NAME) group which received L-NAME as NOS inhibitor, Hemin group which received hemin as HO inducer and Zn protoporphyrin (ZnPP) group which received ZnPP as HO inhibitor. The results of this study demonstrated that there was co-induction as well as co-repression of iNOS and HO-1 gene expression using either the inducers or inhibitors of both enzymes, whereas HO-2 gene expression was found to be upregulated by the use of L-arginine only in L-arginine rat group. HO-2 gene expression was not changed by the use of either HO inducer, suppressor or NOS suppressor. cGMP tissue levels in CC was significantly elevated in rats receiving HO inducer (hemin) as well as in those receiving NOS inducer (arginine) as compared with the control group, with a significant elevation in cGMP levels in hemin group as compared with L-arginine group. The use of hemin appears to be more efficient and dominates the use of arginine in inducing HO activity as well as cGMP tissue levels. These data indicate that HO and its product carbon monoxide (CO) are supervising nitric oxide as a signaling molecule in erectile function. On the other hand, There was a significant decrease in cGMP levels in HO inhibitor and in NOS inhibitor groups with a significant decrease in its levels in ZnPP group as compared with L-NAME group. HO enzymatic activity was significantly elevated in the hemin group, whereas it was significantly decreased in ZnPP and in arginine rat groups in comparison with the other groups. NOS activity was significantly elevated in arginine group and in ZnPP group and it was significantly decreased in L-NAME and in hemin rat groups in comparison with the other rat groups. Conclusion: The use of either NOS or HO inducers can equally enhance erectile function via upregulation of gene expression of the two signaling genes involved in erection as well as through upregulation of the tissue levels of cGMP, the mediator of vasodilatation. Our data indicate that HO/CO system is supervising and dominating nitric oxide as a signaling molecule in erectile function. Thus, induction of HO may have therapeutic implications for management of erectile dysfunction.
关键词：heme oxygenase;nitric oxide;GMP;corpora cavernosa;heme;arginine;erection