Endothelin-1 Synthesis and Receptor-Mediated Activity in Porcine Lymph Vessels

• Published in: The Journal of surgical research 1996-06, Vol.63 (1), p.215-219
• Main Authors: Reeder, Laurie B., Ferguson, Mark K.
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Arginine - analogs & derivatives; Arginine - pharmacology; Biological and medical sciences; Blood vessels and receptors; Bronchi; Endothelin Receptor Antagonists; Endothelins - biosynthesis; Endothelins - pharmacology; Endothelium, Lymphatic - physiology; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Immunohistochemistry; In Vitro Techniques; Lymphatic System - drug effects; Lymphatic System - physiology; Mediastinum; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Muscle, Smooth - physiology; Nitric Oxide Synthase - antagonists & inhibitors; Oligopeptides - pharmacology; omega-N-Methylarginine; Piperidines - pharmacology; Receptor, Endothelin A; Receptors, Endothelin - physiology; Swine; Trachea; Vertebrates: cardiovascular system
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1006/jsre.1996.0250

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 recordedin vitroin fresh porcine tracheobronchial lymph vessel rings in response to the cumulative addition of ET-1 (10−11to 10−6M). ET-1 induced a tonic contraction with peak tension at 3 × 10−7M(mean tension 3731 ± 306 mg; 259 ± 20 percent of response to 65 mMKCl). The addition of specific receptor antagonists (ETA(BQ-610), ETB(BQ-788), or both) blocked the contractile response seen in ET-1 stimulated controls (ETA+ ETB> ETA>> ETB). The response to ET-1 was increased by endothelial damage but was unaffected by the inhibition of NO synthesis byNG-monomethyl-L-arginine (L-NMMA). Endothelial damage altered the ET-1 response in the presence of ETBantagonist but not ETAantagonist. 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.