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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Campo, G. M. Arlotta, M. Squadrito, G. Quartarone, C. Caputi, A. P. Squadrito, F. Ferlito, M. Grimaldi, S. Altavilla, D. Saitta, A. |
| Description | Author Affiliation: Squadrito F ( Institute of Pharmacology, School of Medicine, University of Messina, Italy. squadrito@csnet.it) |
| Abstract | 1. Tumour necrosis factor (TNF-alpha) is a pleiotropic cytokine which is deeply involved in the pathogenesis of splanchnic artery occlusion (SAO) shock. Tacrolimus, formerly known as FK506, is a macrolide antibiotic, that blocks the transcription of several proinflammatory cytokines including TNF-alpha. 2. Male anaesthetized rats were subjected to clamping of the splanchnic arteries for 45 min. This surgical procedure resulted in an irreversible state of shock (SAO shock). Sham operated animals were used as controls. SAO shocked rats had a decreased survival rate (0% at 4 h of reperfusion, while sham shocked rats survived more than 4 h), enhanced serum TNF-alpha concentrations (415+/-12 U ml(-1)), decreased mean arterial blood pressure (MAP), leukopenia and increased ileal leukocyte accumulation studied by means of myeloperoxidase activity (MPO=7.5+/-0.3 U g(-1) tissue). Moreover aortic rings from shocked rats showed a marked hyporeactivity to phenylephrine (PE, 1 nM - 10 microM), reduced responsiveness to acetylcholine (ACh, 10 nM - 10 microM) and increased staining for intercellular adhesion molecule-1 (ICAM-1). Furthermore increased mRNA for TNF-alpha was observed in peritoneal macrophages of SAO shocked rats. 3. Tacrolimus (100 microg kg(-1), 5 min after splanchnic arteries occlusion) increased survival rate (SAO + Tacrolimus = 100% at 4 h of reperfusion), reverted the marked hypotension, reduced serum TNF-alpha (15+/-3 U ml(-1)), ameliorated leukopenia, reduced ileal MPO (0.9+/-0.01 U g(-1) tissue), restored to control values the hyporeactivity to PE. improved the reduced responsiveness to ACh and blunted the enhanced immunostaining for ICAM-1 in the aorta. Finally tacrolimus suppressed cytokine mRNA levels in peritoneal macrophages. 4. The data suggest that tacrolimus may represent a new therapeutic approach in circulatory shock. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 2 |
| Volume Number | 127 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1999-05-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Immunosuppressive Agents Pharmacology Shock Prevention & Control Splanchnic Circulation Physiology Tacrolimus Tumor Necrosis Factor-alpha Antagonists & Inhibitors Animals Blood Pressure Drug Effects Constriction, Pathologic Endothelium, Vascular Pathology Immunohistochemistry Leukocyte Count Macrophages Metabolism Muscle Contraction Muscle, Smooth, Vascular Peroxidase RNA, Messenger Biosynthesis Rats, Sprague-Dawley Reverse Transcriptase Polymerase Chain Reaction Mortality Physiopathology Survival Analysis |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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