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Participation of tumour necrosis factor and nitric oxide in the mediation of vascular dysfunction in splanchnic artery occlusion shock
Author(s) -
Squadrito Francesco,
Altavilla Domenica,
Canale Patrizia,
Ioculano Mariapatrizia,
Campo Giuseppe M.,
Ammendolia Letteria,
Ferlito Marcella,
Zingarelli Basilia,
Squadrito Giovanni,
Saitta Antonino,
Caputi Achille P.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb17118.x
Subject(s) - phenylephrine , shock (circulatory) , medicine , nitric oxide , circulatory system , splanchnic , endocrinology , superior mesenteric artery , mesenteric arteries , anesthesia , omega n methylarginine , endothelium , nitric oxide synthase , artery , blood pressure , hemodynamics
1 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. 2 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 n m ‐10 μ m ) and reduced responsiveness to acetylcholine (ACh lOnM‐lOμ m ). 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 μ m ). 3 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. 4 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.