Endogenous vasopressin increases acute endotoxin shock-provoked gastrointestinal mucosal injury in the rat.
Administration of a low dose of endotoxin (from Escherichia coli, 3 mg kg(-1), i.v.), which does not affect vascular permeability or blood pressure over 1 h, leads to the release of endogenous vasopressin and damage to the mucosal microvasculature. Thus, endogenous vasopressin could be involved in septic shock. In the present study, we investigated the role of endogenous vasopressin in gastrointestinal mucosal injury induced by acute endotoxin shock, which was generated in rats by administering a high dose of E. coli endotoxin (50 mg kg(-1), i.v.). Tissues were removed 15 min after endotoxin. The vasopressin V1 receptor antagonist, d[CH2]5Tyr[Me]arginine-vasopressin (0.2-1 microg kg(-1), i.v.), was injected 10 min before endotoxin. Monastral blue (30 mg kg(-1), i.v.), which stains damaged vasculature, was injected 10 min before autopsy. Endotoxin reduced systemic arterial blood pressure (from 115+/-5 to 42+/-4 mmHg), generated macroscopic and microvascular injury, and elevated plasma vasopressin levels (from 3.4+/-0.2 to 178+/-16 pg ml(-1)). The vasopressin V1 receptor antagonist reduced this macroscopic injury, and in the vasopressin-deficient Brattleboro rat a similar reduction of gastrointestinal mucosal damage was found. Substantial decreases in endotoxin-induced microvascular damage were observed in each tissue, e.g., the gastric Monastral blue staining was reduced by 47+/-3% and 96+/-3% (P < 0.01) after vasopressin V1 receptor antagonist treatment and in Brattleboro rats, respectively. Vasopressin, acting through its V1 receptors, thus appears to be involved in acute endotoxin shock-provoked gastrointestinal injury.
Dept. of Comparative Physiology, Attila József University of Sciences, Szeged, Hungary.
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Varga
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Pávó
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Lamarque
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Szepes
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Kiss
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Karácsony
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László
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László
D000818:Animals; D004731:Endotoxins / Q000633:toxicity*; D005260:Female; D005753:Gastric Mucosa / Q000098:blood supply / Q000473:pathology*; D007413:Intestinal Mucosa / Q000098:blood supply / Q000473:pathology*; D051381:Rats; D011910:Rats, Brattleboro; D017208:Rats, Wistar; D012772:Shock, Septic / Q000473:pathology*; D013045:Species Specificity; D014667:Vasopressins / Q000097:blood / Q000235:genetics / Q000502:physiology*
D004731:Endotoxins; D014667:Vasopressins; C044101:endotoxin, Escherichia coli