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Chronic sildenafil treatment inhibits monocrotaline-induced pulmonary hypertension in rats

Schermuly, Ralph T., Kreisselmeier, Klaus P., Ghofrani, Hossein A., Yilmaz, Huseyin Butrous G., Ermert, Leander, Ermert, Monika, Weissman, Norbert, Rose, Frank, Guenther, Andreas, Walmrath, Dieter, and others. (2004) Chronic sildenafil treatment inhibits monocrotaline-induced pulmonary hypertension in rats. American Journal of Respiratory and Critical care Medicine, 169 (1). pp. 39-45. ISSN 1073-449X. (doi:10.1164/rccm.200302-282OC) (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:12268)

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/10.1164/rccm.200302-282OC

Abstract

Sildenafil, a phosphodiesterase 5 inhibitor, is currently under investigation for therapy of pulmonary hypertension. This study was designed to investigate chronic effects of sildenafil in monocrotaline (MCT)-induced pulmonary hypertension in rats. Four weeks after a single subcutaneous injection of MCT, the animals displayed nearly threefold elevated pulmonary artery pressure and vascular resistance values, with a concomitant decline in central venous oxygen saturation and arterial oxygenation. Marked right heart hypertrophy was evident, and massive thickening of the precapillary artery smooth muscle layer was histologically apparent. Further deterioration of pulmonary hypertension occurred 6 weeks after MCT injection, with some animals dying during this period because of right heart failure. When chronically administered from Days 14-28, slide-nafil significantly increased plasma cyclic guanosine monophosphate and inhibited the development of pulmonary hypertension and right heart hypertrophy, with preservation of gas exchange and systemic arterial pressure. A corresponding efficacy profile was also noted for long-term feeding with sildenafil from Days 28-42. Moreover, the death rate significantly decreased in those animals treated with slide-nafil. We conclude that sildenafil attenuates MCT-induced pulmonary hypertension and cor pulmonale in rats.

Item Type: Article
DOI/Identification number: 10.1164/rccm.200302-282OC
Additional information: pulmonary hypertension; monocrotaline; phosphodiesterase inhibitor; phosphodiesterase; sildenafil NOT IN FILE DOI: 10.1164/rccm.200302-282OC
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: 01 Oct 2008 14:03 UTC
Last Modified: 16 Nov 2021 09:50 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/12268 (The current URI for this page, for reference purposes)

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