Long-term effects of sub-chronic exposure to L-NAME on reproductive system of male rats

Nω-nitro-l-arginine methyl ester (L-NAME) has been utilized as a nitric oxide synthase antagonist for many years in both basic and clinical research settings to assess its therapeutic potential. Though a number of studies have shown the effect of L-NAME on testicular function, the information regarding the reversibility of these effects upon L-NAME withdrawal is limited. In the present study, male rats (68-80 days old) divided randomly into three groups received different doses of L-NAME, i.e. 20 mg/kg bw (L20) and 10 mg/kg bw (L10) in drinking water, and drinking water only (control) through oral gavage daily for three weeks. The rats were monitored for and sacrificed after 60 days of L-NAME treatment termination. The animals had a significantly higher (p < 0.01) mean blood pressure compared to control. Aberrant histological changes were observed in the testes of L-NAME-treated rats. A significant reduction (p < 0.05) in the sperm count and an increase in abnormal sperm morphology (p < 0.05) was observed in L-NAME treated rats. Moreover, the spermatogenic cycle was found to be altered in L-NAME treated rats. No change was observed in serum estradiol levels, while serum testosterone levels were significantly increased (p < 0.05) in L10 and L20 animals. The intra-testicular testosterone was increased significantly (p < 0.01) in L20 animals. A significant decrease (p < 0.05) in superoxide dismutase activity was observed in L20 animals. The sub-chronic exposure to L-NAME resulted in higher mean arterial blood pressure and long-term testicular tissue damage, affecting sperm quality and spermatogenesis.