Estudo dos efeitos da inibição crônica do óxido nítrico na reprodução de ratos machos

Abstract

Nitric Oxide (NO) derived from L-arginine by the nitric oxide synthase (NOS) which is expressed by various isoforms, is considered to be na important messenger molecule in several organ systems including the male genital tract. This study analysed the possible effects of L-NAME (NG-nitro-L-arginine methyl ester), a nonselective NOS inhibitor on testicilar descent; cholinergic stimulation-induced seminal emission; testicular function; sexual behaviour; and on fertility of male Wistar rats. Treatment of 20 days old male rats with L-NAME at 20mg/kg/day for 10 consecutive days caused a significant delay in the testes descent compared to controls that receives only normal saline. This effect of L-NAME was fully reversed in animals pretreated with L-arginine (600mg/kg, s.c.), a substrate for NO biosynthesis, suggesting stimulant drug pilocarpine (0.75 – 3.0 mg/kg, i.p.) induced a dose-related seminal emission. The seminal emission response to 3.0mg/kg of pilocarpine was greatly diminished in atropinized animals, suggesting a cholinomimetic effect. L-NAME, also inhibited the pilocarpine-induced seminal emission which could be reversed by L-arginine (600mg/kg, s.c.). Further, urine analysis for nitrate/nitrite metabolites showed marked alterations in accordance to the drug treatments. These results suggest that NO mediates the inhibitory neurotransmission responsible for seminal emission in pilocarpine stimulated rats. In experiments carried out to verify the effects of chonic NOS inhibition on copulatory behavior, treatment of rats with L-NAME (40mg/kg/day) for a period of one complete spermatogenic cycle caused an inhibitory influence on sexual behavior as evidenced by a increase in the first mount and intromission latencies and marked inhibitions of the intromission and ejaculation frequencies. Chronic NOS inhibition further evidenced impaired testicular function, reflected by decreases in serum levels of testosterone, epididymal sperm counts and sperm abnormalities. The number of females impregnated with males that received chronic L-NAME treatment was highly reduced, resulting in 75% inhibition of fertility. The adverse influence of L-NAME on male infertility could be due to NOS inhibition at both peripheral and central sites causing inhibition of local androgen and/or gonadotropin secretions. These results provide evidence that NO importantly regulates male reproductive processes such as testicular descent, sexual behavior and fertility.