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 nitroglyce rin and of long-term electrical stimulation on relaxations induced by non-adrenergic, non-cholinergic nerve stimulation, exogenous NO, vasoa ctive intestinal polypeptide (VIP) and lemakalim was investigated in t he pig gastric fundus. 2 In physiological salt solution containing 10( -6) M atropine and 4x10(-6) M guanethidine, electrical field stimulati on (40 V, 0.1 ms, 0.5-8 Hz) for periods of 10 s at 5 min intervals (tr ain stimulation) and administration of NO (2x10(-6)-10(-4) M) at 5 min intervals (NO boli) induced frequency-and concentration-dependent tra nsient relaxations, respectively. Continuous electrical field stimulat ion with stepwise increase of the frequency (0.5-8 Hz; cumulative stim ulation) induced frequency-dependent sustained relaxations. VIP (10(-7 ) M), lemakalim (10(-5) M) and an infusion of WO induced a sustained r elaxation. 3 Pretreatment for 30 min with 5 x 10(-4) M nitroglycerin r educed the relaxations induced by train and cumulative stimulation, bu t 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. Admini stration of 3 x 10(-4) M N-G-nitro-L-arginine methyl ester after 10, 2 0 or 30 min reversed the relaxation to a similar extent (approximately 70%). Previous long-term electrical stimulation at 4 Hz for 30 min di d not affect the responses to stimulation, NO and VIP. 5 These results illustrate that nitroglycerin can induce a postjunctional tolerance t o nitrergic stimuli in the pig gastric fundus but evidence for a preju nctional inhibition of neuronal NO synthase by NO was not obtained.