Effects of endothelin on spontaneous contractions in lymph vessels.
A mode of action of endothelin (ET) on spontaneous contractions was investigated in ring preparations of isolated bovine mesenteric lymphatics. ET-1 at concentrations between 10(-10) and 10(-9) M caused a dose-dependent increase in the frequency of spontaneous contractions. The specific ET(A)-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 without the endothelium. Mechanical denudation of the lymphatic endothelial cells produced a significant potentiation of the ET-induced positive chronotropic effect. BQ-3020 (10(-8)-10(-7) M), a selective ET(B)-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 the BQ-3020-induced negative chronotropic and inotropic effects. The ET-1-induced positive chronotropic effect was potentiated by pretreatment with N(omega)-nitro-L-arginine methyl ester (L-NAME) (10(-5) M) but unaffected by aspirin (10(-5) M). Additional treatment with L-arginine (10(-4) M) completely reversed the L-NAME-mediated potentiation of the ET-induced chronotropic effect. These results suggest that stimulation of ET(A) receptors on the lymphatic smooth muscles causes a positive chronotropic effect on the spontaneous contractions, and stimulation of ET(B) receptors on the lymphatic endothelial cells induces a release of nitric oxide, which results in the chronotropic and inotropic effects on spontaneous contractions in isolated bovine mesenteric lymphatics.
Sakai
H
H
The First Department of Physiology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
Ikomi
F
F
Ohhashi
T
T
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D002417:Cattle; D002909:Chronobiology Phenomena / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004357:Drug Synergism; D019332:Endothelin-1 / Q000494:pharmacology*; D016232:Endothelins / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008208:Lymphatic System / Q000187:drug effects* / Q000502:physiology*; D008643:Mesentery; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology
D004338:Drug Combinations; D019332:Endothelin-1; D016232:Endothelins; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D010456:Peptides, Cyclic; C075771:BQ 3020; D001120:Arginine; D001241:Aspirin; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D019331:NG-Nitroarginine Methyl Ester