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. 2014 Sep;17(9):710-5.

Effect of thoracic epidural blockade on hypoxia-induced pulmonary arterial hypertension in rats

Shi-Huan Yu  1 , Jing-Ying Chen  2 , Yi-Mei Zhang  2 , Gui-Wei Jiao  2 , Feng-Qi Liu  2 , Ling-Fei Kong  2
Affiliations

Effect of thoracic epidural blockade on hypoxia-induced pulmonary arterial hypertension in rats

Shi-Huan Yu et al. Iran J Basic Med Sci. 2014 Sep.

Abstract

Objectives: The present study was aimed to investigate the influence of thoracic epidural blockade on hypoxia-induced pulmonary hypertension in rats.

Materials and methods: Forty eight Wistar rats were randomly divided into 4 equal groups, named normoxia hypoxia hypoxia/ ropivacaine and hypoxia/saline. Animals were placed in a hypoxia chamber and instrumented with epidural catheters at the thoracic level. Rats were injected with saline or ropivacaine. Haemodynamic measurements included pulmonary artery pressure and right ventricular hypertrophy. Degree of pulmonary vascular remodeling was determined by Hematoxylin and Eosin (HE) staining. Serum cyclic GMP (cGMP) and TNF-α were measured using radioimmuno assay. Real-time PCR and western boltting were employed to examine the expression of cAMP responding-element binding protein (CREB).

Results: We found that the thoracic epidural blockade significantly decreased chronic hypoxia-induced pulmonary hypertension and vascular remodeling in rats. Ropivacaine-treated rats exhibited significantly lower mean pulmonary artery pressure (mPAP), ratio of right ventricular weight to left ventricular plus septal weight (RV/(LV+S)) and wall thickness of pulmonary artery compared with those of control rats. Hypoxia-induced increase in levels of serum cGMP and TNF-α was reversed by thoracic epidural blockade. Moreover, hypoxia increased expression of CREB at mRNA and protein levels which could be suppressed by thoracic epidural blockade.

Conclusion: Thoracic epidural blockade reduced mPAP and serum level of TNF-α and increased cGMP. The treatment reversed upregulated expression of CREB at mRNA and protein production.

Keywords: CREB; Hypoxia; Pulmonary arterial hypertension; Thoracic epidural blockade TNF-α.

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Figures

Figure 1.
Figure 1.
Effects of TEB on chronic hypoxia-induced pulmonary vascular structure remodeling of rats. Hematoxylin and Eosin staining of pulmonary arterioles. (A) Normoxia (B) Hypoxia (C) Hypoxia/ ropivacaine (D) Hypoxia/ saline
Figure 2.
Figure 2.
Effect of TEB on CREB expression in lung tissue of hypoxia-exposed rats. Animals were exposed to either normoxia or hypoxia atmosphere for 3 weeks and treated with TEB or saline. After treatments, total protein extraction was carried out to determine CREB by immunoblotting.. Lane 1: normoxia; lane 2: hypoxia; Lane 3: hypoxia/ ropivacaine and lane 4: hypoxia/ saline. β-actin was used as internal control. CREB: cAMP respondingelement binding protein
See this image and copyright information in PMC

References

    1. Lin MJ, Leung GP, Zhang WM, Yang XR, Yip KP, Tse CM, Sham JS. Chronic hypoxia-induced upregulation of store-operated and receptor-operated ca2+ channels in pulmonary arterial smooth muscle cells: A novel mechanism of hypoxic pulmonary hypertension. Circ Res . 2004; 95:496–505. - PubMed
    1. Yu L, Quinn DA, Garg HG, Hales CA. Cyclin-dependent kinase inhibitor p27kip1 but not p21waf1/cip1 is required for inhibition of hypoxia-induced pulmonary hypertension and remodeling by heparin in mice. Circ Res . 2005; 97:937–945. - PubMed
    1. Soon E, Holmes AM, Treacy CM, Doughty NJ, Southgate L, Machado RD, Trembath RC, Jennings S, Barker L, Nicklin P, Walker C, Budd DC, Pepke-Zaba J, Morrell NW. Elevated levels of inflammatory cytokines predict survival in idiopathic and familial pulmonary arterial hypertension. Circulation . 2010; 122:920–927. - PubMed
    1. Murray F, MacLean MR, Pyne NJ. Increased expression of the cgmp-inhibited camp-specific (pde3) and cgmp binding cgmp-specific (pde5) phosphodiesterases in models of pulmonary hypertension. Br J Pharmacol . 2002; 137:1187–1194. - PMC - PubMed
    1. Yu L, Hales CA. Effect of chemokine receptor cxcr4 on hypoxia-induced pulmonary hypertension and vascular remodeling in rats. Respir Res . 2011; 12:21. - PMC - PubMed

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