Effects of chronic L-DOPA administration on neurogenic and endothelium-dependent relaxation responses in rabbit corpus cavernosum

Abstract

Background: Dopamine is a crucial central neurotransmitter that plays a fundamental role in the autonomic and somatic components of penile reflexes in animals and humans. Similar to the erectile responses of dopamine, systemic administration of L-DOPA induces yawning and penile erection in some species. The possible effects of L-DOPA on nitric oxide (NO)-dependent and-independent non-adrenergic non-cholinergic (NANC) relaxation responses mediated by electrical field stimulation (EFS) and endothelium-dependent relaxation were investigated in this study. Methods: Thirty-two adult albino male rabbits, in two- and four-week-treatment groups, were divided into three subgroups: control group (saline-injected) (n = 4), 3 mg/kg/day (low dose) L-DOPA-injected groups (n = 6) and 12 mg/kg/day (high dose) L-DOPA-injected groups (n = 6). After the intraperitoneal injection treatments, the corpus cavernosum tissues were placed in organ bath chambers. The EFS-mediated responses, and the concentration-response curve to carbachol, sodium nitroprusside (SNP), sildenafil were assessed. Results: The two-week treatment with high-dose L-DOPA decreased the NO-dependent NANC relaxation responses, while there was no change in the low-dose two- and four-week treatment groups. The NO independent NANC relaxation responses in the two-week groups decreased, and the responses in the four-week groups were unchanged when compared to the controls. The relaxation responses to carbachol showed no differences among all groups except for the high-dose four-week L-DOPA group. The relaxation responses of SNP and sildenafil were increased in all of the treatment groups when compared to the controls. Conclusions: The observed increases in SNP- and sildenafil-induced responses, along with the decreased EFS-mediated responses, suggest increased sensitivity in the NO-signalling pathway following L-DOPA administration. (C) 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.