Endothelin-1 synthesis and receptor-mediated activity in porcine lymph vessels.
Endothelin-1 (ET-1) is a potent vasoconstrictor of blood vessels and interacts with nitric oxide (NO) to regulate vascular tone. We hypothesized that ET-1 may modulate lymph vessel tone via local synthesis, receptor-mediated vasoconstriction, and interaction with NO. Serial sections obtained from formalin-fixed porcine mediastinal tissue, incubated with either ET-1 or von Willebrand factor antibody and stained with avidin-biotin complex and peroxidase, demonstrated ET-1 in lymphatic vascular endothelium. Isometric tension was recorded in vitro in fresh porcine tracheo-bronchial lymph vessel rings in response to the cumulative addition of ET-1 (10(-11) to 10(-6) M). ET-1 induced a tonic contraction with peak tension at 3 x 10(-7) M (mean tension 3731 +/- 306 mg; 259 +/- 20 percent of response to 65 mM KCl). The addition of specific receptor antagonists (ET(A) (BQ-610), ET(B) (BQ-788), or both) blocked the contractile response seen in ET-1 stimulated controls (ET(A) + ET(B) > ET(A)>> ET(B). The response to ET-1 was increased by endothelial damage but was unaffected by the inhibition of NO synthesis by N (G)-monomethyl-L-arginine (L-NMMA) Endothelial damage altered the ET-1 response in the presence of ET(B) antagonist but not ET(A) antagonist. ET-1 is a potent endothelium-derived vasoconstrictor of lymph vessels. Its effects are mediated through specific receptors, are not importantly modulated by NO, but may be modified by release of other endothelium-derived relaxing factors. We conclude that lymph vessel tone may be regulated by ET-1.
Reeder
L B
LB
Section of Thoracic Surgery, Department of Surgery, University of Chicago, Illinois 60637, USA.
Ferguson
M K
MK
D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001980:Bronchi; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000096:biosynthesis* / Q000494:pharmacology*; D004729:Endothelium, Lymphatic / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008208:Lymphatic System / Q000187:drug effects / Q000502:physiology*; D008482:Mediastinum; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009842:Oligopeptides / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000502:physiology*; D013552:Swine; D014132:Trachea; D019323:omega-N-Methylarginine
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D010880:Piperidines; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; C087220:BQ 610; D019323:omega-N-Methylarginine; C086539:BQ 788; D001120:Arginine; D019001:Nitric Oxide Synthase