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

Francesco Squadrito, Domenica Altavilla, Patrizia Canale, Mariapatrizia Ioculano, Giuseppe M. Campo, Letteria Ammendolia, Marcella Ferlito, Basilia Zingarelli, Giovanni Squadrito, Antonino Saitta, Achille P. Caputi

Research output: Contribution to journalArticlepeer-review

Abstract

Splanchnic artery occlusion (SAO) shock is characterized by irreversible circulatory failure. Tumour necrosis factor (TNF‐α) may affect the 1‐arginine/nitric oxide (NO) pathway, thus contributing to the cardiovascular derangements of circulatory shock. We investigated the contribution of both TNF‐α and the 1‐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‐α. Furthermore, aortic rings from shocked rats showed a marked hyporeactivity to phenylephrine (PE 1 nm‐10 μm) and reduced responsiveness to acetylcholine (ACh lOnM‐lOμm). Endothelium‐denuded aortic rings had also a marked hyporeactivity to phenylephrine, which was restored to control values by in vitro administration of N° nitro‐1‐arginine‐methyl ester (1‐NAME 10 μm). In vivo administration of cloricromene (2 mg kg−1, i.v.), an inhibitor of TNF‐α biosynthesis, increased survival, enhanced mean arterial blood pressure and reduced macrophage and serum levels of TNF‐α. 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. Our results suggest that TNF‐α alters both endothelial and muscular L‐arginine/nitric oxide pathways which in turn produce vascular dysfunction in SAO shock. 1994 British Pharmacological Society

Original languageEnglish (US)
Pages (from-to)1153-1158
Number of pages6
JournalBritish Journal of Pharmacology
Volume113
Issue number4
DOIs
StatePublished - Dec 1994

Keywords

  • Cytokine
  • L‐arginine‐NO pathway
  • endothelium
  • impaired vascular reactivity

ASJC Scopus subject areas

  • Pharmacology

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