Interactions of pro-inflammatory and vasoactive mediators with nitric oxide in the regulation of rat vascular permeability during laparotomy

• Published in: European journal of pharmacology 2000-08, Vol.402 (1), p.193-197
• Main Authors: Pávó, Imre, Pozsár, József, Morschl, Éva, Nemcsik, János, László, Ferenc, Whittle, Brendan J.R
• Format: Article
• Language: English
• Subjects: Abdomen; Albumins - metabolism; Animals; Biological and medical sciences; Capillary Permeability - physiology; Enzyme Inhibitors - pharmacology; Inflammation - physiopathology; Laparotomy; Leukotrienes; Leukotrienes - physiology; Male; Medical sciences; Neutrophil granulocytes; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide (NO); Nitric Oxide - physiology; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase Type III; Platelet Activating Factor - physiology; Platelet-activating factor (PAF); Rats; Rats, Wistar; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the digestive system; Thromboxanes; Thromboxanes - physiology; Vascular endothelium; Vascular permeability; Vasopressin
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(00)00490-8

Inhibition of constitutive nitric oxide (NO) synthases by administration of N G-nitro- l-arginine methyl ester ( l-NAME) during abdominal laparotomy provokes extensive vascular leakage in the rat gastrointestinal tract, assessed by the extravasation of [ 125I]human serum albumin. In the present study, the role of vasoactive or neutrophil-derived pro-inflammatory mediators in this process has been investigated. Administration of the thromboxane synthase inhibitor, 1-benzyl-imidazole (BZI, 25–50 mg kg −1, s.c.), the platelet-activating factor (PAF) receptor antagonist, 3-[4-(2-chlorophenyl)-9-methyl-6 H-thienol-[3,2-f][1,2,4]-triazolo-[4,3-a][1,4]-diazepine-2-yl]-1-(4-morpholynil)-1-propionate (WEB 2086; 0.5–1 mg kg −1, s.c.), the 5-lipoxygenase synthase inhibitor, N-(4-benzyloxybenzyl)-acetohydroxamic acid (BW A137C; 4–20 mg kg −1, s.c.) or the vasopressin pressor receptor antagonist ([Mca 1,Tyr(Me) 2,Arg 8]vasopressin/Manning peptide; 0.01–0.2 μg kg −1, s.c.) dose-dependently reduced the intestinal plasma leakage provoked by l-NAME (5 mg kg −1, s.c.), following a 5-cm abdominal laparotomy in anaesthetised rats. These findings suggest that constitutive NO synthase effectively counteracts the damaging actions on microvascular integrity of mediators, including thromboxanes, PAF, leukotrienes and vasopressin, released during surgical intervention.