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Beneficial effects of sildenafil to alleviate pulmonary hypertension after 2 and 4‐week chronic hypoxia
Author(s) -
Milano Giuseppina,
Joncic Ana,
Morel Sandrine,
Samaja Michele,
Vassalli Giuseppe,
Segesser Ludwig Karl
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1173.8
Subject(s) - sildenafil , enos , medicine , hypoxia (environmental) , right ventricular hypertrophy , pulmonary hypertension , muscle hypertrophy , cardiology , nitric oxide , snap , nitric oxide synthase , endocrinology , chemistry , oxygen , computer graphics (images) , organic chemistry , computer science
Aim. We investigated whether sildenafil alleviates the cardiovascular and pulmonary alterations induced by 2‐ or 4‐week chronic hypoxia (CH). Methods. Rats were exposed to room air (21% O2, N), CH (10% O2) for 2 and 4 weeks, with and without treatment with Sildenafil (1.4 mg/Kg/day, ip) (n=7/group). At the end of the exposure, we measured right ventricular hypertrophy (right to left plus septum weight, RV/LV+S), pulmonary wall thickness index (WTI), right and left systolic ventricular pressures (RVSP and LVSP, respectively) and endothelial nitric oxide synthase (eNOS) proteins. Results. CH increased RV/LV+S (p<0.05) and WTI (p<0.01) after 2 and 4 weeks. Treatment with sildenafil attenuated both parameters after 2 weeks (p<0.05) and after 4 weeks hypoxia (p=0.01). RVSP was higher in CH than N rats (p=0.01). Treatment with sildenafil attenuated this parameter irrespectively of the duration of hypoxia. By contrast, CH did not change LVSP after either 2 or 4 weeks. The phosphorylated form of eNOS decreased in CH hearts (p<0.05). Treatment with Sildenafil increased the phosphorylated form of eNOS to normoxic values irrespectively of duration of hypoxia. Conclusion. Treatment with sildenafil provides an efficient strategy for the management of cardiac and pulmonary hypertrophy during CH, irrespectively of the duration until 4 weeks, presumably via increased phosphorylation of eNOS.