ABSTRACT
ABSTRACT Background: Pulmonary arterial hypertension (PAH) is a serious disease characterized by the progressive elevation of the pulmonary arterial resistance, leading to the right ventricular failure and death. Objective: To evaluate the effect of rapamycin (RAPA), a potent cell-cycle inhibitor, on exercise capacity, right ventricular hypertrophy and pulmonary vascular remodelling on rats. Methods: A total of 39 nine-week-old male Wistar rats (160-240 g) were divided into three groups: the control (n = 10), PAH control (n = 15) and PAH-RAPA (n = 14) groups. On the 1st day, 60 mg/kg monocrotaline was injected intraperitoneally to induce PAH in the PAH control group and PAH-RAPA groups. On the 21st day, 3 mg/kg/day RAPA was started orally, and the animals were followed for 35 days. On the 35th day, the exercise capacity of the rats was analysed through a modified forced swimming test. After measuring their right ventricular systolic pressure using an open-chest method, their hearts and lungs were excised and analysed histopathologically for right ventricular hypertrophy and pulmonary vascular remodelling. Results: Rapamycin treatment provided limited and insignificant improvements in exercise capacity, right ventricular systolic pressure and right ventricular hypertrophy of the rats. However, there was significant recovery in the rats' pulmonary artery muscular layer thickness with the RAPA treatment (p < 0.049). On the 35th day, the mortality rate was 0% in the control group, 53.1% in the PAH control group and 42.9% in the PAH-RAPA group. No statistically significant decrease was observed in their mortality rates with the RAPA treatment (p > 0.16); however, a significant recovery was noted in terms of the rats' median life span (p < 0.006). Conclusion: Pulmonary artificial hypertension is a progressive disease that is not curable with current therapies. Rapamycin may have the potential to reverse vascular remodelling and prolong life expectancy in cases of pulmonary hypertension.
ABSTRACT
Objective: Sildenafil is a selective and potent inhibitor of cyclic guanosine monophosphate specific phosphodiesterase-5 and has anti-inflammatory effects. The aim of the study was to evaluate the effects of sildenafil on smoke-induced lung inflammation. Material and Methods: Twenty-nine Wistar-Albino rats were enrolled into 3 groups as control, smoker and sildenafil groups. Smoker and sildenafil groups were exposed to cigarette smoke for 2 hours per day for 8 weeks. Sildenafil 10 mg/kg/day was administered to the sildenafil group by nasogastric lavage after smoke exposure. The degree of lung inflammation was scored histopathologically for each group. Results: The inflammation score was 7.25±0.93 in the control group, 8.18±1.21 in the smoker group and 7.08±1.66 in the sildenafil group. There was a non-significant decrease of inflammation score in sildenafil group with respect to control or smoker groups. While there was no significant difference of oedema, hyperemia, hemorrhage and mononuclear cell infiltration scores among the groups, it was found that the thickness of interalveolar septum and alveolar distortion was decreased in sildenafil group. However this decrease was not statistically significant. Conclusion: This study suggests that sildenafil might reduce smoke-induced inflammation in rat lungs. Future studies are needed in order to investigate the clinical effectiveness of this finding in smoking related lung diseases.