Effects of endothelin on spontaneous contractions in lymph vessels

A mode of action of endothelin (ET) on spontaneous contractions was investi gated in ring preparations of isolated bovine mesenteric lymphatics. ET-1 a t concentrations between 10(-10) and 10(-9) M caused a dose-dependent incre ase in the frequency of spontaneous contractions. The specific ETA-receptor antagonist BQ-123 (5 x 10(-7) M) caused a significant inhibition of the ET -1-induced positive chronotropic effect in the ring preparations with and w ithout the endothelium. Mechanical denudation of the lymphatic endothelial cells produced a significant potentiation of the ET-induced positive chrono tropic effect. BQ-3020(10(-8)-10(-7 M)), a selective ETB-receptor agonist, induced dose dependently negative chronotropic and inotropic effects on the spontaneous contractions in the ring preparations with intact endothelium. Mechanical removal of the endothelium caused a significant reduction of th e BQ-3020-induced negative chronotropic and inotropic effects. The ET-1-ind uced positive chronotropic effect was potentiated by pretreatment with N-om ega-nitro-L-arginine methyl ester (L-NAME) (10(-5) M) but unaffected by asp irin (10(-5) M). Additional treatment with L-arginine (10(-4) M) completely reversed the L-NAME-mediated potentiation of the ET-induced chronotropic e ffect. These results suggest that stimulation of ETA receptors on the lymph atic smooth muscles causes a positive chronotropic effect on the spontaneou s contractions, and stimulation of ETB receptors on the lymphatic endotheli al cells induces a release of nitric oxide, which results in the chronotrop ic and inotropic effects on spontaneous contractions in isolated bovine mes enteric lymphatics.