Effects of nitric oxide synthase blockade on the acute response of the reproductive axis to ethanol in pubertal male rats

The effects of ethanol (EtOH) and nitric oxide (NO) are well known in the a dult male rat reproductive axis. In the present study, we investigate the e ffects of EtOH, NO, and their interaction on key genes and reproductive hor mone levels in mid- (45-day) and late pubertal (55-day) male rats. Using th ree different NO synthase blockers-N omega-nitro-L-arginine methyl ester (L -NAME), Nb-nitro-L-arginine (L-NA), and 7-nitroindazole-we show that it is possible to block, in part, some of the disruptive effects of EtOH. I-NAME totally prevented the EtOH-induced fall in serum testosterone in both 45- a nd 55-day-old rats (p < 0.05 and p < 0.001, respectively). On the other han d, the D-NAME, an inactive isomer of L-NAME, did not protect testosterone f rom suppression caused by EtOH. Similarly, I-NA and 7-nitroindazole prevent ed the suppression of testosterone caused by EtOH in 55-day-old animals (p < 0.001 L-NA and p < 0.05 for 7-nitroindazole), but not in the 45-day-old r ats. Serum luteinizing hormone (Ln) was significantly reduced by EtOH in al l the studies in both age groups. I-NAME (but not D-NAME) and L-NA prevente d this inhibition in 55-day-old animals (p < 0.001 fur I-NAME and p < 0.01 for L-NA). However, only L-NA was able to prevent the effects of EtOH on LW in the 45-day-old rats. 7-Nitroindazole was unable to prevent the decrease in LH in either age group. Despite changes in the other reproductive hormo nes, there were no consistent changes in hypothalamic concentrations of eit her LH releasing hormone (LHRH) or its precursor, pro-LHRH. No treatment ca used any change in steady-state levels of beta-LH mRNA. There were no consi stent changes in pro-LHRH mRNA; but, interestingly, in 45-day-old rats, L-N A given with or without EtOH lead to a significant fall in LHRH gene expres sion. Our findings indicate that the acute suppressive effects of EtOH on t he hypothalamic-pituitary-gonadal axis of the purbertal male rat can be at least partially prevented by NO synthase blockade.