Spontaneous release of nitric oxide inhibits electrical, Ca2+ and mechanical transients in canine gastric smooth muscle

Abstract

1. In canine antrum, rhythmic electrical activity consists of a rapid upstroke phase followed by a plateau depolarization. In response to slow waves, cytosolic Ca2+ ([Ca2+]cyt) and tension increased. 2. Addition of sodium nitroprusside (SNP, 0.5 microM) decreased the amplitude of the plateau phase of slow waves without significant effects on the upstroke depolarization. SNP also inhibited changes in [Ca2+]cyt and tension associated with the plateau potential. SNP induced a negative chronotropic effect at concentrations above 0.1 microM. 3. Similar to the effects of SNP, illumination of muscles during slow waves with ultraviolet (UV) light caused premature repolarization. UV illumination is known to release NO in some tissues. 4. L-NG-monomethyl-arginine (L-NMMA, 300 microM), Methylene Blue (MB, 5 microM) and oxyhaemoglobin (oxy-Hb, 5 microM) increased the force of contractions. In contrast, L-arginine (L-Arg, 300 microM) decreased contractile force and antagonized the effects of L-NMMA. 5. During the upstroke phase, SNP caused a small reduction in [Ca2+]cyt and a large reduction in force, suggesting that SNP caused a decrease in Ca2+ sensitivity. 6. In muscles permeabilized by alpha-toxin, cyclic GMP (100 microM) and UV illumination inhibited Ca(2+)-induced contraction (at pCa 5.5). 7. These data suggest that NO or NO-related compounds are spontaneously released in gastric muscles. These agents have two effects on excitation-contraction coupling: (i) inhibition (directly and/or indirectly) of the voltage-dependent Ca2+ channels that participate in the plateau phase of slow waves, and (ii) reduction in the Ca2+ sensitivity of the contractile element.