Prevention of bronchial hyperreactivity in a rat model of precapillary pulmonary hypertensionReport as inadecuate




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Respiratory Research

, 12:58

First Online: 01 December 2011Received: 07 December 2010Accepted: 27 April 2011

Abstract

BackgroundThe development of bronchial hyperreactivity BHR subsequent to precapillary pulmonary hypertension PHT was prevented by acting on the major signalling pathways endothelin, nitric oxide, vasoactive intestine peptide VIP and prostacyclin involved in the control of the pulmonary vascular and bronchial tones.

MethodsFive groups of rats underwent surgery to prepare an aorta-caval shunt ACS to induce sustained precapillary PHT for 4 weeks. During this period, no treatment was applied in one group ACS controls, while the other groups were pretreated with VIP, iloprost, tezosentan via an intraperitoneally implemented osmotic pump, or by orally administered sildenafil. An additional group underwent sham surgery. Four weeks later, the lung responsiveness to increasing doses of an intravenous infusion of methacholine 2, 4, 8 12 and 24 μg-kg-min was determined by using the forced oscillation technique to assess the airway resistance Raw.

ResultsBHR developed in the untreated rats, as reflected by a significant decrease in ED50, the equivalent dose of methacholine required to cause a 50% increase in Raw. All drugs tested prevented the development of BHR, iloprost being the most effective in reducing both the systolic pulmonary arterial pressure Ppa; 28%, p = 0.035 and BHR ED50 = 9.9 ± 1.7 vs. 43 ± 11 μg-kg in ACS control and iloprost-treated rats, respectively, p = 0.008. Significant correlations were found between the levels of Ppa and ED50 R = -0.59, p = 0.016, indicating that mechanical interdependence is primarily responsible for the development of BHR.

ConclusionsThe efficiency of such treatment demonstrates that re-establishment of the balance of constrictor-dilator mediators via various signalling pathways involved in PHT is of potential benefit for the avoidance of the development of BHR.

Electronic supplementary materialThe online version of this article doi:10.1186-1465-9921-12-58 contains supplementary material, which is available to authorized users.

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