Mechanism of relaxation induced by K+ and nicotine in dog duodenal longitudinal muscle.

Dog duodenal longitudinal muscle strips precontracted with bradykinin responded to K+ (10 mM) with a transient relaxation, which was abolished by tetrodotoxin and oxyhemoglobin, but not influenced by atropine, ouabain and apamin. The induced relaxation was suppressed by treatment with 10(-5) M NG-nitro-L-arginine (L-NNA) a nitric oxide synthesis inhibitor, but not by the D-enantiomer. The inhibitory effect was antagonized by L- but not D-arginine. High concentrations (20 mM or higher) of K+ produced a relaxation followed by a sustained contraction; nicardipine abolished the contraction, but did not alter the relaxation. Nicotine produced a contraction, which was converted to a relaxation by atropine. The relaxant response was abolished by tetrodotoxin, hexamethonium and oxyhemoglobin, but was unaffected by timolol and phentolamine. L-NNA suppressed the relaxation, and L-arginine reversed the inhibition. The addition of K+ (20 mM) increased the content of cyclic GMP in the strips, the effect being prevented by tetrodotoxin and L-NNA. These findings suggest that K+ selectively stimulates the nonadrenergic inhibitory nerve, whereas nicotine stimulates both the excitatory cholinergic and inhibitory nerves. Nitric oxide released from the inhibitory nerve appears to transmit information to duodenal smooth muscle by increasing the production of cyclic GMP.