Abstract
INTRODUCTION: Vascular hyporeactivity is an important problem associated with sepsis. Although the mechanism involves inflammatory pathway activation, specific therapeutic approaches have not been defined. Glutamine (Gln) has been shown to provide some anti-inflammatory effects and improve outcomes in sepsis. Here, we tested the hypothesis that Gln could reduce Escherichia coli lipopolysaccharide (LPS)-induced vascular hyporeactivity and evaluated the role of heat-shock protein 70 (HSP70) induction in this process. METHODS: Twenty-four male Sprague-Dawley rats were divided into control, LPS shock, and alanyl-Gln dipeptide+LPS shock (Ala-Gln+LPS) groups. Six hours after administration of LPS, phenylephrine (PE) (0.5 to approximately 2.5 microg/kg) was applied intravenously to all groups, and the percentage increase in mean arterial pressure (MAP) was detected in the respective groups. The concentration-response curve of PE was obtained in tension experiments, and the average values of PE maximum efficacy (Emax) and median effective dose (EC50) were calculated. The plasma concentrations of malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) were detected in all groups. The expressions of HSP70 from heart, liver, lung, and aorta were also assayed in all groups. RESULTS: The maximal percentage increase in MAP induced by PE was significantly reduced to 12.7% in the LPS shock group (P < 0.05) and was restored to 15.6% in the Ala-Gln+LPS group (P < 0.05), whereas the control group was 24.7%. The average values of PE Emax and EC50 were significantly impaired in the LPS shock group (P < 0.05) but partially restored in the Ala-Gln+LPS group (P < 0.05). The expressions of HSP70 from the heart, aorta, lung, and liver were much higher in the Ala-Gln+LPS group than those in the LPS shock group (P < 0.05). The plasma concentrations of TNF-alpha, IL-6, and MDA were much lower in the Ala-Gln+LPS group than those in the LPS shock group. CONCLUSION: Gln effectively improves vascular reactivity by inducing the expression of HSP70, reducing inflammatory cytokine release and peroxide biosynthesis in LPS shock rats. These results suggest that Gln has a potentially beneficial therapeutic effect for septic shock patients.