The effect of chronic ethanol administration on nitric oxide-mediated responses in rat isolated trachea preparation

1. In the present study, we investigated the effect of chronic ethanol administration on nitric oxide (NO)-mediated responses in rat isolated trachea preparation. 2. Ethanol was given to rats in a modified liquid diet for 21 days. Isolated tracheal rings were then used to obtain responses to electrical field stimulation (EFS) after precontraction with 100 microM histamine. The parameters of field stimulation were as follows: supramaximal voltage of 50 V, 0.5 ms duration, 10-s train; 0.5, 1, 3, 5, 10, 20, 30 and 50 Hz at 2-min intervals. The effects of L-and D-arginine (10(-6) M) on the responses to field stimulation (10-20 Hz) were studied. In other experiments, we tested the effects of N(omega)-nitro-L-arginine methyl ester (L-NAME, 10(-6)-10(-5) M) and SIN-1 (10(-6)-10(-5) M) on the responses to field stimulation. 3. Electrical field stimulation induced relaxation responses in the tracheal rings precontracted with histamine from control- and ethanol-treated rats. The relaxation responses induced by EFS were significantly reduced in the tracheal rings precontracted with histamine from ethanol dependent group. The responses induced by EFS in both groups were completely abolished by tetrodotoxin (1 microM), but unaffected by hexamethonium (1 microM). Incubation with D-arginine did not cause statistically significant increases in relaxation responses to EFS in both groups. L-Arginine (10(-6) M) caused statistically significant increases in relaxation responses to EFS in control rats, but not in ethanol dependent rats. Incubation with L-NAME (10(-6)-10(-5) M) caused statistically significant inhibition of the relaxation responses to EFS in both groups. SIN-1 (10(-6)-10(-5) M) induced significantly increase in relaxation responses to EFS in both groups. 4. Our results suggest that the possible mechanism responsible for inhibition of tracheal inhibitory responses to EFS in ethanol-dependent rats may be a reduction in production of NO and in the uptake of L-arginine.