Skip to main content

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

Weissmann, Norbert, Gerigk, Boris, Kocer, Ozlem, Nollen, Matthias, Hackemack, Sascha, Ghofrani, Hossein A., Schermuly, Ralph T., Butrous, Ghazwan S., Schulz, Andreas, Roth, Markus, and others. (2007) Hypoxia-induced pulmonary hypertension: Different impact of iloprost, sildenafil, and nitric oxide. Respiratory Medicine, 101 (10). pp. 2125-2132. ISSN 0954-6111. (doi:10.1016/j.rmed.2007.05.025) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:12306)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided.
Official URL:
http://dx.doi.org/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
DOI/Identification number: 10.1016/j.rmed.2007.05.025
Uncontrolled keywords: pulmonary; hypertension; right heart failure; iloprost; NO; sildenafil
Subjects: R Medicine > R Medicine (General)
Divisions: Divisions > Division for the Study of Law, Society and Social Justice > School of Social Policy, Sociology and Social Research
Depositing User: M.P. Stone
Date Deposited: 04 Aug 2008 11:58 UTC
Last Modified: 16 Nov 2021 09:50 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/12306 (The current URI for this page, for reference purposes)

University of Kent Author Information

Butrous, Ghazwan S..

Creator's ORCID:
CReDIT Contributor Roles:
  • Depositors only (login required):

Total unique views for this document in KAR since July 2020. For more details click on the image.