The effects of acetylcholine (ACh) on spontaneous contractions in isolated bovine mesenteric lymph vessels were investigated. ACh ranging from 3 x 10(-8) M to 10(-5) M produced dose-dependent negative chronotropic and inotropic effects on the spontaneous contractions. In the lymph vessels without endothelium, ACh at the same concentration range had no significant effect on the spontaneous contractions. Atropine (10(-9) and 10(-8) M) caused a parallel shift to the right of the dose-chronotropic response curve for ACh. The pA2 value of atropine to ACh in the negative chronotropic effect was 8.90 +/- 0.20 (n = 6). Aspirin (10(-5) M) produced no significant inhibition of the ACh-induced negative chronotropic and inotropic effects. NG-monomethyl-L-arginine (L-NMMA; 3 x 10(-5) M) significantly suppressed the ACh-induced negative responses on spontaneous contractions. In the same lymphatic segments, L-arginine (10(-4) M) reversed completely the inhibition by L-NMMA of the ACh-induced responses. These results suggest that low concentrations of ACh produce negative chronotropic and inotropic effects on spontaneous contractions in bovine mesenteric lymphatics and that the responses may be mediated by nitric oxide or its related compound released from the endothelial cells through activation of low-affinity muscarinic receptors.
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