COMPARISON OF RELAXATIONS EVOKED BY PHOTOACTIVATION OF NO-CONTAINING COMPOUNDS AND NITRERGIC NERVE-STIMULATION IN 5-HYDROXYTRYPTAMINE-CONTRACTED AND POTASSIUM-CONTRACTED RAT GASTRIC FUNDUS

1. The aim of the present study was to further investigate our earlier proposal of liberation of nitric oxide (NO) by photoactivation of mol ecules containing NO or NO2, which in turn relaxes gastric smooth musc le, and to determine whether presynaptic and/or postsynaptic NO-mediat ed relaxation is affected differently by the degree of membrane depola rization in rat gastric fundus smooth muscle. 2. During contraction of rat gastric fundus with 5-hydroxytryptamine (5-HT, 10 mu M), low (K+, 25 mM) and high potassium (K+, 65.4 mM), relaxation responses to nitr ergic nerve stimulation, photo activation of caged NO compounds (strep tozotocin [STZ], N-omega-nitro-L-arginine-methylacetate [L-NAME], N-om ega-nitro-D-arginine-methylacetate [D-NAME]), and sodium nitroprusside (SNP) were compared. 3. Nitrergic nerve (presynaptic) stimulation and photoactivation (postsynaptic) of all caged NO compounds produced rap id, transient and reversible relaxation of 5-HT and low-K+-contracted tissues. However, when contractions were induced by high K+, the relax ation induced by nerve stimulation was abolished, whereas relaxations induced by photoactivated NO compounds were significantly (P<0.01) red uced. 4. The relaxation induced by sodium nitroprusside (SNP), but not papaverine, was also diminished in high-K+-contracted tissues. The ma gnitude of photoactivated NO induced relaxation was related to the amo unt of NO release, light intensity and concentration of compounds. 5. The evidence that photoactivated NO-induced relaxation is mediated by cGMP comes from the observation that zaprinast, but not forskolin, pot entiated the relaxation. 6. It is concluded that rat gastric smooth mu scle relaxes to photoactivation of NO or NO2-carrying molecules via NO , and it appears that degree of membrane depolarization may be a criti cal factor in dissociating the response to presynaptic and postsynapti c NO mediated relaxation in this muscle. (C) 1998 Elsevier Science Inc .