Simvastatin decreases nitric oxide overproduction and reverts the impaired vascular responsiveness induced by endotoxic shock in rats

Lipopolysaccharides (LPS) can be used to induce experimental endotoxic shock, which is characterized by a significant decrease in mean arterial pressure (MAP) and a decreased vasoconstrictor response that have been attributed to excessive nitric oxide production. Inhibitors of 3-hydroxy-3-methylglut...

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Published in:Shock (Augusta, Ga.) Ga.), 2004-03, Vol.21 (3), p.271-275
Main Authors: GIUSTI-PAIVA, Alexandre, MARTINEZ, Maria Regina, CESTARI FELIX, Jorge Vinicius, ALVES DA ROCHA, Maria Jose, CAPELLARI CARNIO, Evelin, KAGOHARA ELIAS, Lucila Leico, ANTUNES-RODRIGUES, Jose
Format: Article
Language:English
Subjects:
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Animals
Biological and medical sciences
Blood Pressure
Cholesterol - blood
Dose-Response Relationship, Drug
Endothelium, Vascular - drug effects
Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology
Inflammation
Intensive care medicine
Lipopolysaccharides - metabolism
Male
Medical sciences
Nitrates - metabolism
Nitric Oxide - metabolism
Pressure
Protein Isoforms
Rats
Rats, Wistar
Shock, Septic - pathology
Simvastatin - pharmacology
Time Factors
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Summary:Lipopolysaccharides (LPS) can be used to induce experimental endotoxic shock, which is characterized by a significant decrease in mean arterial pressure (MAP) and a decreased vasoconstrictor response that have been attributed to excessive nitric oxide production. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), in addition to lowering serum cholesterol levels, exert many pleiotropic effects, including anti-inflammatory action. In the present study, we investigated the effect of simvastatin, an HMG-CoA reductase inhibitor, on the production of nitric oxide and the cardiovascular response to LPS. Male Wistar rats were pretreated with different doses of simvastatin (10, 20, 40, and 80 mg/kg, i.p.) or saline 20 min before i.v. injection of LPS (1.5 mg/kg) or saline (control). MAP was continuously recorded and nitrate plasma concentration was determined during the 6-h experimental session at 1-h intervals. The pressor response to phenylephrine (1 microg/kg) was evaluated before and 6 h after LPS administration. In the LPS-treated group, there was a time-dependent increase in nitrate plasma concentration (P
ISSN:1073-2322
1540-0514
DOI:10.1097/10.shk.0000115756.74059.ce