Chronic sildenafil treatment inhibits monocrotaline-induced pulmonary hypertension in rats

Schermuly, Ralph T. and Kreisselmeier, Klaus P. and Ghofrani, Hossein A. and Yilmaz, Huseyin Butrous G. and Ermert, Leander and Ermert, Monika and Weissman, Norbert and Rose, Frank and Guenther, Andreas and Walmrath, Dieter and Seeger, Werner and Grimminger, Friedrich (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. (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)

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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
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: Faculties > Science Technology and Medical Studies > Kent Institute of Medicine and Health Sciences (KIMHS)
Depositing User: M.P. Stone
Date Deposited: 01 Oct 2008 14:03
Last Modified: 16 Apr 2014 08:35
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