PMID- 26725912 OWN - NLM STAT- MEDLINE DCOM- 20161017 LR - 20181202 IS - 2042-7158 (Electronic) IS - 0022-3573 (Linking) VI - 68 IP - 1 DP - 2016 Jan TI - Consequence of hyperhomocysteinaemia on alpha1-adrenoceptor-mediated contraction in the rat corpus cavernosum: the role of reactive oxygen species. PG - 63-75 LID - 10.1111/jphp.12486 [doi] AB - OBJECTIVES: Our main objective was to investigate the mechanisms underlying the effects of hyperhomocysteinaemia (HHcy) on contractile response mediated by alpha1-adrenoceptors in the rat corpus cavernosum. METHODS: Concentration-response curves for phenylephrine (PE) were obtained in strips of corpus cavernosum, in absence or after incubation with tiron, tempol or polyethylene glycol (PEG)-catalase combined or not with tempol. We also measured the superoxide anion (O2(-)) and hydrogen peroxide (H2O2) generation, superoxide dismutase (SOD) and catalase activity and alpha-actin expression in rat corpus cavernosum from both groups. KEY FINDINGS: HHcy increased PE-induced contraction in cavernosal strips. Tiron, PEG-catalase or tempol increased PE-induced contraction in strips from control rats, but it was not altered by tiron or PEG-catalase in HHcy rats, whereas tempol reduced this response. The combination of PEG-catalase and tempol did not alter the contractile response to PE in both groups. HHcy increased O2(-) generation and SOD activity, whereas H2O2 concentration was reduced. Finally, HHcy did not alter catalase activity or expression of alpha-actin. CONCLUSIONS: The major new finding from this study is that HHcy induced a marked increase in PE-induced contraction in rat corpus cavernosum by a mechanism that involves increased O2(-) generation and it could play a role in the pathogenesis of erectile dysfunction associated with HHcy. CI - (c) 2015 Royal Pharmaceutical Society. FAU - Coco, Hariane AU - Coco H AD - Departament of Pharmacology, Faculdade de Medicina de Ribeirao Preto, Ribeirao Preto, SP, Brazil. FAU - Pernomian, Larissa AU - Pernomian L AD - Laboratory of Vascular Injury, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Ribeirao Preto, SP, Brazil. FAU - Marchi, Katia C AU - Marchi KC AD - Departament of Pharmacology, Faculdade de Medicina de Ribeirao Preto, Ribeirao Preto, SP, Brazil. FAU - Gomes, Mayara S AU - Gomes MS AD - Laboratory of Vascular Injury, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Ribeirao Preto, SP, Brazil. FAU - de Andrade, Claudia R AU - de Andrade CR AD - Department of Pathology and Legal Medicine, Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, SP, Brazil. FAU - Ramalho, Leandra N Z AU - Ramalho LN AD - Nucleus of Applied Bioprospection and Molecular Research, Faculdades Inta, Fortaleza, CE, Brazil. FAU - Tirapelli, Carlos R AU - Tirapelli CR AD - Laboratory of Pharmacology, Escola de Enfermagem de Ribeirao Preto, Ribeirao Preto, SP, Brazil. FAU - de Oliveira, Ana M AU - de Oliveira AM AD - Laboratory of Vascular Injury, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Ribeirao Preto, SP, Brazil. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160104 PL - England TA - J Pharm Pharmacol JT - The Journal of pharmacy and pharmacology JID - 0376363 RN - 0 (Actins) RN - 0 (Reactive Oxygen Species) RN - 0 (Receptors, Adrenergic, alpha-1) RN - 0 (catalase-polyethylene glycol) RN - 11062-77-4 (Superoxides) RN - 1WS297W6MV (Phenylephrine) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - BBX060AN9V (Hydrogen Peroxide) RN - EC 1.11.1.6 (Catalase) SB - IM MH - Actins/metabolism MH - Animals MH - Catalase/metabolism MH - Erectile Dysfunction/metabolism MH - Hydrogen Peroxide/metabolism MH - Hyperhomocysteinemia/*metabolism MH - Male MH - Muscle Contraction/drug effects/physiology MH - Muscle, Smooth/drug effects/metabolism MH - Penis/drug effects/*metabolism MH - Phenylephrine/pharmacology MH - Polyethylene Glycols/metabolism MH - Rats MH - Rats, Wistar MH - Reactive Oxygen Species/*metabolism MH - Receptors, Adrenergic, alpha-1/*metabolism MH - Superoxides/metabolism OTO - NOTNLM OT - corpus cavernosum OT - hyperhomocysteinaemia OT - alpha1-adrenergic agonist and reactive oxygen species EDAT- 2016/01/05 06:00 MHDA- 2016/10/19 06:00 CRDT- 2016/01/05 06:00 PHST- 2015/06/11 00:00 [received] PHST- 2015/09/12 00:00 [accepted] PHST- 2016/01/05 06:00 [entrez] PHST- 2016/01/05 06:00 [pubmed] PHST- 2016/10/19 06:00 [medline] AID - 10.1111/jphp.12486 [doi] PST - ppublish SO - J Pharm Pharmacol. 2016 Jan;68(1):63-75. doi: 10.1111/jphp.12486. Epub 2016 Jan 4.