title: Role of endothelin receptors and relationship with nitric oxide synthase in impaired erectile response in diabetic rats.
abstract: To evaluate the protective role of bosentan (BOS), an endothelin-1 (ET-1) receptor antagonist, and to show the changes in rats with experimentally induced diabetic erectile dysfunction (ED), a total of 24 albino Wistar rats were allocated into four groups. Group 1 was the healthy group and Group 2 had diabetes mellitus (DM) induced by intraperitoneal injection of 60 mg kg-1streptozotocin (STZ). Following the establishment of DM, Group 3 and Group 4 were treated with oral BOS doses of 50 mg kg-1and 100 mg kg-1, respectively, for 60 days. At the end of the treatment, we evaluated yawning and erection response to apomorphine treatment and then the animals were sacrificed. ET-1, eNOS, iNOS, tumour necrosis factor (TNF)-α, ET-RA and ET-RB mRNA expressions were analysed in cavernosal tissue. It was observed that yawning and erection response decreased in the diabetic group; however, both of these improved with BOS treatment. While ET-1, TNF-α and iNOS gene expressions increased, eNOS, ET-RA and ET-RB gene expressions decreased in the DM group compared to the healthy group. DM has a negative impact on cavernosal tissue blood flow through activating vasoconstrictor mediators in cavernosal tissue. BOS regulates significantly eNOS, iNOS and TNF-α expressions in a dose-dependent manner.
authors.affiliation: Department of Urology, Memorial Sisli Hospital, Istanbul, Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Alkan
authors.affiliation: Faculty of Medicine, Department of Pharmacology, Ataturk University, Erzurum, Turkey.
authors.forename: R A
authors.initials: RA
authors.lastname: Ugan
authors.affiliation: Department of Urology, Memorial Sisli Hospital, Istanbul, Turkey.
authors.forename: M M
authors.initials: MM
authors.lastname: Basar
authors.affiliation: Faculty of Medicine, Department of Pharmacology, Ataturk University, Erzurum, Turkey.
authors.forename: Z
authors.initials: Z
authors.lastname: Halici
authors.affiliation: Faculty of Veterinary, Department of Pharmacology and Toxicology, Ataturk University, Erzurum, Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Karakus
authors.affiliation: Department of Urology, Memorial Sisli Hospital, Istanbul, Turkey.
authors.forename: M D
authors.initials: MD
authors.lastname: Balbay
authors.affiliation: Faculty of Pharmacy, Department of Biochemistry, Ibrahim Cecen University, Agri, Turkey.
authors.forename: H
authors.initials: H
authors.lastname: Un
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D000077300:Bosentan; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D018491:Dopamine Agonists / Q000494:pharmacology; D065128:Endothelin Receptor Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D019332:Endothelin-1 / Q000378:metabolism; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000209:etiology*; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010410:Penile Erection / Q000187:drug effects*; D010413:Penis / Q000098:blood supply / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000378:metabolism; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018491:Dopamine Agonists; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D001058:Apomorphine; D000077300:Bosentan
keywords: Bosentan; diabetes mellitus; erectile dysfunction; rat