TY - JOUR
T1 - Participation of tumour necrosis factor and nitric oxide in the mediation of vascular dysfunction in splanchnic artery occlusion shock
AU - Squadrito, Francesco
AU - Altavilla, Domenica
AU - Canale, Patrizia
AU - Ioculano, Mariapatrizia
AU - Campo, Giuseppe M.
AU - Ammendolia, Letteria
AU - Ferlito, Marcella
AU - Zingarelli, Basilia
AU - Squadrito, Giovanni
AU - Saitta, Antonino
AU - Caputi, Achille P.
PY - 1994/12
Y1 - 1994/12
N2 - 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
AB - 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
KW - Cytokine
KW - L‐arginine‐NO pathway
KW - endothelium
KW - impaired vascular reactivity
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U2 - 10.1111/j.1476-5381.1994.tb17118.x
DO - 10.1111/j.1476-5381.1994.tb17118.x
M3 - Article
C2 - 7889268
AN - SCOPUS:0028149638
SN - 0007-1188
VL - 113
SP - 1153
EP - 1158
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 4
ER -