Interactions of pro-inflammatory and vasoactive mediators with nitric oxide in the regulation of rat vascular permeability during laparotomy.
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-6H-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 microg 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.
Endocrine Unit, Medical Faculty, University of Szeged, Szeged, Hungary.
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I
Pávó
J
J
Pozsár
E
E
Morschl
J
J
Nemcsik
F
F
László
B J
BJ
Whittle
D000418:Albumins / Q000378:metabolism; D000818:Animals; D002199:Capillary Permeability / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007249:Inflammation / Q000503:physiopathology*; D007813:Laparotomy; D015289:Leukotrienes / Q000502:physiology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D010972:Platelet Activating Factor / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013931:Thromboxanes / Q000502:physiology
D000418:Albumins; D004791:Enzyme Inhibitors; D015289:Leukotrienes; D010972:Platelet Activating Factor; D013931:Thromboxanes; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019331:NG-Nitroarginine Methyl Ester