Consequence of hyperhomocysteinaemia on α1-adrenoceptor-mediated contraction in the rat corpus cavernosum: the role of reactive oxygen species

• Published in: Journal of pharmacy and pharmacology 2016-01, Vol.68 (1), p.63-75
• Main Authors: Côco, Hariane, Pernomian, Larissa, Marchi, Katia C., Gomes, Mayara S., de Andrade, Cláudia R., Ramalho, Leandra N. Z., Tirapelli, Carlos R., de Oliveira, Ana M.
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Animals; Catalase - metabolism; corpus cavernosum; Erectile Dysfunction - metabolism; Hydrogen Peroxide - metabolism; hyperhomocysteinaemia; Hyperhomocysteinemia - metabolism; Male; Muscle Contraction - drug effects; Muscle Contraction - physiology; Muscle, Smooth - drug effects; Muscle, Smooth - metabolism; Penis - drug effects; Penis - metabolism; Phenylephrine - pharmacology; Polyethylene Glycols - metabolism; Rats; Rats, Wistar; Reactive Oxygen Species - metabolism; Receptors, Adrenergic, alpha-1 - metabolism; Superoxides - metabolism; α1-adrenergic agonist and reactive oxygen species
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1111/jphp.12486

Objectives Our main objective was to investigate the mechanisms underlying the effects of hyperhomocysteinaemia (HHcy) on contractile response mediated by α1‐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 α‐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 α‐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.