title: Epigallocatechin-3-gallate ameliorates erectile function in aged rats via regulation of PRMT1/DDAH/ADMA/NOS metabolism pathway.
abstract: Aging-related ED is predominantly attributed to neurovascular dysfunction mediated by NO suppression and increased oxidative stress in penis. The alterations of protein arginine methyltransferases 1 (PRMT1)/dimethylarginine dimethylaminohydrolase (DDAH)/asymmetrical dimethylarginine (ADMA)/NO synthase (NOS) pathway regulate NO production in the vascular endothelium. Epigallocatechin-3-gallate (EGCG) is one of the most abundant and antioxidative ingredients isolated from green tea. In the present study, 40 Sprague-Dawley rats were randomly distributed into four groups: one young rat group and three aged rat groups treated with daily gavage feedings of EGCG at doses of 0, 10 mg kg-1 and 100 mg kg-1 for 12 weeks, respectively. Erectile function was assessed by electrical stimulation of the cavernous nerves with intracavernous pressure (ICP) measurement. After euthanasia, penile tissue was investigated using Western blot and ELISA to assess the PRMT1/DDAH/ADMA/NOS metabolism pathway. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were detected by colorimetry. We also evaluated smooth muscle contents. The ratio of maximal ICP and mean systemic arterial pressure (MAP) was markedly higher in EGCG-treated aged rats than in untreated aged rats. We found that DDAH1 and DDAH2 were expressed in cavernosal tissue, and they were downregulated in corpora of aged rats. The administration of EGCG upregulated the expression and activity of DDAH. In contrast, EGCG treatment downregulated the expression of PRMT1 and ADMA content. Moreover, EGCG-treated rats showed an improvement in smooth muscle expression, the ratio of smooth muscle cell/collagen fibril, SOD activity, and MDA levels when compared with untreated aged rats.
authors.affiliation: Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China.
authors.forename: Ke-Qin
authors.initials: KQ
authors.lastname: Zhang
authors.affiliation: Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China.
authors.forename: Ding-Qi
authors.initials: DQ
authors.lastname: Sun
authors.affiliation: Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
mesh_terms: D000375:Aging; D000581:Amidohydrolases / Q000187:drug effects*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives* / Q000187:drug effects; D062186:Arterial Pressure / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006152:Cyclic GMP / Q000378:metabolism; D007172:Erectile Dysfunction / Q000188:drug therapy*; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000254:growth & development; D019001:Nitric Oxide Synthase / Q000187:drug effects*; D010410:Penile Erection / Q000187:drug effects; D010413:Penis / Q000187:drug effects / Q000378:metabolism; D011484:Protein-Arginine N-Methyltransferases / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D000072105:Superoxide Dismutase-1 / Q000187:drug effects / Q000378:metabolism
chemical_list: D000975:Antioxidants; C018524:N,N-dimethylarginine; D002392:Catechin; D001120:Arginine; C045651:epigallocatechin gallate; D019001:Nitric Oxide Synthase; C000606292:Sod1 protein, rat; D000072105:Superoxide Dismutase-1; C541817:PRMT1 protein, rat; D011484:Protein-Arginine N-Methyltransferases; D000581:Amidohydrolases; C059999:dimethylargininase; D006152:Cyclic GMP