Participation of tumour necrosis factor and nitric oxide in the mediation of vascular dysfunction in splanchnic artery occlusion shock - PubMed (original) (raw)

Participation of tumour necrosis factor and nitric oxide in the mediation of vascular dysfunction in splanchnic artery occlusion shock

F Squadrito et al. Br J Pharmacol. 1994 Dec.

Abstract

1. Splanchnic artery occlusion (SAO) shock is characterized by irreversible circulatory failure. Tumour necrosis factor (TNF-alpha) may affect the L-arginine/nitric oxide (NO) pathway, thus contributing to the cardiovascular derangements of circulatory shock. 2. We investigated the contribution of both TNF-alpha and the L-arginine/nitric oxide pathway to the vascular dysfunction of SAO shock. Anaesthetized rats, subjected to total occlusion of the superior mesenteric artery and the coeliac trunk for 45 min developed a severe shock state (SAO shock) resulting in a fatal outcome within 75-90 min after the release of occlusion. Sham operated animals were used as controls. SAO shocked rats had also a marked hypotension and enhanced macrophage and serum levels of TNF-alpha. Furthermore, aortic rings from shocked rats showed a marked hyporeactivity to phenylephrine (PE 1 nM-10 microM) and reduced responsiveness to acetylcholine (ACh 10 nM-10 microM). Endothelium-denuded aortic rings had also a marked hyporeactivity to phenylephrine, which was restored to control values by in vitro administration of NG nitro-L-arginine-methyl ester (L-NAME 10 microM). 3. In vivo administration of cloricromene (2 mg kg-1, i.v.), an inhibitor of TNF-alpha biosynthesis, increased survival, enhanced mean arterial blood pressure and reduced macrophage and serum levels of TNF-alpha. Furthermore, aortic rings from shocked rats treated with cloricromene exhibited a greater contractile response to phenylephrine and improved responsiveness to ACh when compared to aortic rings from vehicle-treated SAO shocked rats. 4. Our results suggest that TNF-alpha alters both endothelial and muscular L-arginine/nitric oxide pathways which in turn produce vascular dysfunction in SAO shock.

PubMed Disclaimer

Similar articles

Cited by

References

    1. J Immunol. 1980 Oct;125(4):1671-7 - PubMed
    1. Am J Physiol. 1994 Apr;266(4 Pt 2):H1512-5 - PubMed
    1. Nature. 1987 Jun 11-17;327(6122):524-6 - PubMed
    1. Circ Shock. 1988;24(1):43-53 - PubMed
    1. Biochem Biophys Res Commun. 1988 Jun 30;153(3):1251-6 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources