INDOMETHACIN AND THROMBOXANE A(2) PROSTAGLANDIN H-2 ANTAGONIST SQ29,548 IMPAIR IN-VITRO CONTRACTIONS OF AORTIC RINGS OF EX-VIVO TREATED LIPOPOLYSACCHARIDE RATS

Lipopolysaccharide treated rats (25 mg/kg i.v.) were killed after 60 m in and rat aortic rings were mounted in an isolated organ bath for mea surement of isometric contractions in response to phenylephrine (0.01- 10 mu M) or potassium chloride (10 mM). Aortic rings from lipopolysacc haride-treated rats showed reduced contractility to phenylephrine and potassium chloride when compared to those from saline-treated rats, In domethacin 10 mu M, added in vitro further impaired phenylephrine-indu ced contraction of aortic rings from lipopolysaccharide ex vivo treate d rats but was ineffective on aortic rings from saline treated rats. A similar pattern was observed when potassium chloride was used, Admini stration in vitro of thromboxane A(2) receptor antagonist SQ29,548 gav e a similar effect to indomethacin. Aortic rings collected from rat tr eated in vivo with dexamethasone (10 mg/kg) showed a reduction in phen ylephrine induced contractions that was not further reduced by in vitr o treatment with indomethacin (10 mu M). Similarly, when rat aortic ri ngs were incubated in vitro (60 min) with lipopolysaccharide (0.4 mg/m l) a reduction of phenylephrine- and potassium chloride-induced contra ction was observed, but addition of either indomethacin or SQ29,548 di d not further reduce contraction. Our results suggest that under these experimental conditions, in the early phase of endotoxin shock, synth esis of cyclooxygenase products (such as endoperoxides or thromboxane A(2)) occurs probably as a compensatory mechanism to lipopolysaccharid e induced hypocontractility from the interaction, in vivo, between lip opolysaccharide, endothelium, circulating cells and vascular smooth mu scles.