Effect of nitroglycerin and long-term electrical stimulation on nitrergic relaxation in the pig gastric fundus.

1. The effect of incubation with the nitric oxide (NO) donor nitroglycerin and of long-term electrical stimulation on relaxations induced by non-adrenergic, non-cholinergic nerve stimulation, exogenous NO, vasoactive intestinal polypeptide (VIP) and lemakalim was investigated in the pig gastric fundus. 2. In physiological salt solution containing 10(-6) M atropine and 4 x 10(-6) M guanethidine, electrical field stimulation (40 V, 0.1 ms, 0.5-8 Hz) for periods of 10 s at 5 min intervals (train stimulation) and administration of NO (2 x 10(-6)-10(-4) M) at 5 min intervals (NO boli) induced frequency- and concentration-dependent transient relaxations, respectively. Continuous electrical field stimulation with stepwise increase of the frequency (0.5-8 Hz, cumulative stimulation) induced frequency-dependent sustained relaxations. VIP (10(-7) M), lemakalim (10(-5) M) and an infusion of NO induced a sustained relaxation. 3. Pretreatment for 30 min with 5 x 10(-4) M nitroglycerin reduced the relaxations induced by train and cumulative stimulation, but also the relaxant responses to NO, both when given in boli or as an infusion. The relaxations to VIP and lemakalim were not influenced by pretreatment with nitroglycerin. 4. Long-term electrical stimulation at 4 Hz for 40 min induced a sustained relaxation of the tissues. Administration of 3 x 10(-4) M N(G)-nitro-L-arginine methyl ester after 10, 20 or 30 min reversed the relaxation to a similar extent (approximately 70%). Previous long-term electrical stimulation at 4 Hz for 30 min did not affect the responses to stimulation, NO and VIP. 5. These results illustrate that nitroglycerin can induce a postjunctional tolerance to nitrergic stimuli in the pig gastric fundus but evidence for a prejunctional inhibition of neuronal NO synthase by NO was not obtained.