Constitutive nitric oxide modulates the injurious actions of vasopressin on rat intestinal microcirculation in acute endotoxaemia.
The administration of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 5 mg/kg s.c.) concurrently with Escherichia coli endotoxin (3 mg/kg i.v.) increased vascular permeability and caused mucosal damage in the rat intestine 1 h later. The vasopressin V1 receptor antagonist, [Mca1,Tyr(Me)2, Arg8]vasopressin (0.01-0.2 microgram/kg s.c., 15 min before endotoxin) dose-dependently reduced this damage. These results suggest a beneficial role of NO, counteracting the injurious vascular actions of endogenous vasopressin, in maintaining intestinal mucosal integrity in acute endotoxaemic states.
László
F
F
Department of Pharmacology, Wellcome Research Laboratories, Beckenham, Kent, UK.
Whittle
B J
BJ
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects*; D003106:Colon / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004731:Endotoxins / Q000008:administration & dosage / Q000633:toxicity*; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D007082:Ileum / Q000187:drug effects; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014667:Vasopressins / Q000378:metabolism / Q000494:pharmacology
D065092:Antidiuretic Hormone Receptor Antagonists; D004731:Endotoxins; C089517:vasopressin, 1-(2-mercapto-2,2-(cyclopentamethylene)propionic acid)-2-(O-methyl)Tyr-8-Arg-; D014667:Vasopressins; D001127:Arginine Vasopressin; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester