Effect of lithium on endothelium-dependent and neurogenic relaxation of rat corpus cavernosum: Role of nitric oxide pathway

Introduction: Some studies have reported erectile dysfunction in patients receiving lithium through a mechanism that has not yet been defined. The aim of the present study was to verify the effect of acute lithium administration on the nonadrenergic noncholinergic (NANC)- and endothelium-mediated relaxation of rat isolated corpus cavernosum. Materials and methods: The isolated rat corporeal strips were precontracted with phenylephrine hydrochloride (7.5 mu M) and electrical field stimulation (EFS) was applied at different frequencies (2, 5, 10, and 15 Hz) to obtain NANC-mediated relaxation or relaxed by adding cumulative doses of acetylcholine (10 nM-1 mM) to obtain endothelium-dependent relaxation in the presence or absence of lithium (0.3, 0.5, 1, and 5 mM). Also, effects of combining lithium (0.3 mM) with 30 nM and 0.1 nM L-NAME (an NO synthase inhibitor) on NANG and acetylcholine-mediated relaxation was investigated, respectively. Moreover, effects of combining lithium (1 mM) with 0.1 mM and 10 AM L-arginine (a precursor of NO) on NANG and endothelium-mediated relaxation was assessed, respectively. Also, the effect of lithium (1 mM) on relaxation to sodium nitroprusside (SNP; 1 nM-1 mM), an NO donor, was investigated. Results: The NANC-mediated relaxation was significantly (P < 0.001) reduced by 1 and 5 mM, but not by 0.3 and 0.5 mM lithium. Lithium significantly (P < 0.001) attenuated the maximum response to acetylcholine in a concentration-dependent manner. Combination of lithium (0.3 mM) with 30 and 0.1 nM L-NAME, which separately had a minimum effect on NANG and endothelium-mediated relaxation, significantly (P < 0.001) reduced the NANG and endothelium-mediated relaxation, respectively. Although L-arginine at 10 AM and 0.1 mM did not alter the relaxant responses to acetylcholine and EFS, it improved the inhibition by lithium (1 mM) of relaxant responses to acetylcholine and EFS, respectively. Also, SNP produced similar concentration-dependent relaxations from both groups. Discussion: Our experiments indicated that lithium likely by interfering with NO pathway in both endothelium and nitrergic nerve can result in impairment of both the endothelium- and NANC-mediated relaxation of rat corpus cavernosum. (c) 2006 Elsevier Inc. All rights reserved.