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GW24-e1289 Atorvastatin decreases nitric oxide production and restore vascular responsiveness impaired by LPS in rats
  1. Li Xiaoyan,
  2. Zhang Ping
  1. The Third Affiliated Hospital of Sun Yat-sen University

Abstract

Objectives Lipopolysaccharides (LPS) were found in the outer membrane of Gram-negative bacteria and be used to induce experimental endotoxic shock, which could decrease vasoconstrictor response, produce excessive nitric oxide and decrease in mean arterial pressure (MAP). The aim of this study was to investigate the effect of atorvastatin on producing nitric oxide and regulating vasoconstrictor response to LPS.

Methods Male Wistar rats were divided into three group: LPS groups (LPS (1.5 mg/kg,i.v); atorvastatin group (80 mg/kg, i.p. + LPS (1.5 mg/kg,i.v)) and healthy controls rats (saline alone). During the 6h experimental session at 1h intervals, all rats were continuously recorded MAP; tested nitrate plasma concentration and evaluated vascular responsiveness to phenylephrine (1 mg/kg) before and after LPS administration.

Results There was more significant increase in nitrate plasma concentration; decrease of MAP and the vascular responsiveness to phenylephrine in the LPS-treated group than control group (plasma nitrate (uM): 287 ± 9.5 vs 25.6 ± 3.2; MAP(mmHg): 79.5 ± 6.4 vs 113.7 ± 8.6; vascular responsiveness to Phe (mmHg): 28.6 ± 3.2 vs 46.5 ± 5.6, P < 0.01, respectively). Nitrate plasma concentration and vascular responsiveness to phenylephrine could be significantly ameliorated in atorvastatin pretreated rats (plasma nitrate (uM): 132.5 ± 6.8; vascular responsiveness to Phe (mmHg): 43.2 ± 6.3, P < 0.01). However, atorvastatin did not affect the decrease of MAP induced by LPS(MAP(mmHg): 82.5 ± 7.3P > 0.05).

Conclusions These results suggest that atorvastatin, a HMG-CoA reductase inhibitor proved to be an effective pharmacological agent against cardiovascular collapse and mortality in endotoxin shock, by means of reducing nitrate plasma concentration and recovers vascular responsiveness.

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