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Evidence for an endothelium‐derived hyperpolarizing factor in the superior mesenteric artery from rats with cirrhosis
Author(s) -
Barriere Eric,
Tazi Khalid A.,
Rona JeanPierre,
Pessione Fabienne,
Heller Jörg,
Lebrec Didier,
Moreau Richard
Publication year - 2000
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2000.19290
Subject(s) - apamin , charybdotoxin , iberiotoxin , mesenteric arteries , acetylcholine , endothelium , medicine , endocrinology , hyperpolarization (physics) , phenylephrine , endothelium derived hyperpolarizing factor , vasodilation , chemistry , nitric oxide , potassium channel , anesthesia , artery , organic chemistry , nuclear magnetic resonance spectroscopy , blood pressure
In cirrhosis, in splanchnic arteries, endothelium‐dependent relaxation may persist even if overactive nitric oxide synthase (NOS) and cyclooxygenase (COX) are inhibited. In normal arteries, a significant endothelium‐dependent relaxation to acetylcholine persists after NOS/COX inhibition. This relaxation is caused by smooth muscle cell (SMC) membrane hyperpolarization, which is sensitive to a combination of the potassium channel blockers apamin and charybdotoxin, and is mediated by an endothelium‐derived hyperpolarizing factor (EDHF). The aim of this study was to detect EDHF and evaluate its pathophysiologic role in isolated superior mesenteric arteries from cirrhotic rats. Arterial rings were obtained and exposed to N w ‐nitro‐L‐arginine (L‐NNA, a NOS inhibitor) and indomethacin (a COX inhibitor). Acetylcholine‐induced membrane potential responses and concentration‐response curves to the relaxant of acetylcholine were obtained with and without apamin plus charybdotoxin. Acetylcholine‐induced responses were measured in certain rings from endothelium‐denuded arteries. Contractions caused by the α 1 ‐adrenoceptor agonist phenylephrine were obtained in cirrhotic and normal rings with and without apamin and charybdotoxin. Significant acetylcholine‐induced, endothelium‐dependent, apamin‐ and charybdotoxin‐sensitive, SMC membrane hyperpolarization and relaxation were found. An apamin‐ and charybdotoxin‐sensitive hyporesponsiveness to the contractile action of phenylephrine was found in cirrhotic rings. In conclusion, in cirrhotic rats, in the superior mesenteric artery exposed to NOS/COX‐inhibitors, an EDHF exists that may replace NOS/COX products to induce endothelium‐dependent arterial relaxation.