Hypoxia-induced pulmonary hypertension: Different impact of iloprost, sildenafil, and nitric oxide

Weissman, N. and Gerigk, B. and Kocer, O. and Nollen, M. and Hackemack, S. and Ghofrani, H.A. and Schermuly, R.T. and Butrous, G. and Schulz, A. and Roth, M. and Seeger, W. and Grimminger, F. (2007) Hypoxia-induced pulmonary hypertension: Different impact of iloprost, sildenafil, and nitric oxide. Respiratory Medicine, 101 (10). pp. 2125-2132. ISSN 0954-6111. (The full text of this publication is not available from this repository)

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Official URL
10.1016/j.rmed.2007.05.025

Abstract

Objectives: Chronic alveolar hypoxia induces pulmonary hypertension, evident from elevated pulmonary artery pressure (PAP), pulmonary vascular resistance, right ventricular hypertrophy (RVH), and increased muscularization of the pulmonary vasculature. Additionally, the vasoconstrictor response to acute hypoxia (HPV) may be reduced in the remodeled vasculature. However, no direct comparison of different treatments on the various parameters characterizing pulmonary hypertension has been performed yet. Against this background, we compared the effects of inhaled NO, infused iloprost, a stable prostacyclin analogue, and oral sildenafil, a phosphodiesterase 5 inhibitor, on hypoxia-induced pulmonary hypertension. Methods: Exposure of rabbits to chronic hypoxia (FiO(2) = 0.10) for 42 days. Treatment with infused iloprost, oral sildenafil, and inhaled nitric oxide. Results: We quantified PAP, pulmonary vascular resistance, RVH, vascular remodeling, vasoreactivity, and the strength of HPV. Chronic hypoxia resulted in an increase in (a) the right ventricle/(left ventricle+septum) ratio from 0.26 +/- 0.01 to 0.44 +/- 0.01, (b) PAP, and (c) the degree of muscularization from 14.0 +/- 4.0% to 43.5 +/- 5.3%. Treatment with iloprost and sildenafil, but not with NO, prevented the increase in muscularization. In contrast, RVH was strongly inhibited by sildenafil, whereas NO had some minor, and iloprost had no effect. Only iloprost reduced PAP compared to NO and sildenafil. The downregulation of HPV was abrogated only by NO. Conclusion: We demonstrated (a) that the parameters characterizing hypoxia-induced pulmonary hypertension are not functionally linked, (b) that the downregulation of HPV under chronic hypoxia can be prevented by inhaled NO but not by sildenafil and iloprost, and (c) that iloprost is particularly effective in preventing vascular remodeling and sildenafil in preventing RVH. (C) 2007 Published by Elsevier Ltd.

Item Type: Article
Uncontrolled keywords: pulmonary; hypertension; right heart failure; iloprost; NO; sildenafil
Subjects: R Medicine > R Medicine (General)
Divisions: Faculties > Science Technology and Medical Studies > Kent Institute of Medicine and Health Sciences (KIMHS)
Depositing User: M.P. Stone
Date Deposited: 04 Aug 2008 11:58
Last Modified: 04 Aug 2008 11:58
Resource URI: http://kar.kent.ac.uk/id/eprint/12306 (The current URI for this page, for reference purposes)
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