The Extracellular Signal‐Regulated Kinase Is Involved in the Effects of Sildenafil on Pulmonary Vascular Remodeling |
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| Authors: | Zhen Zeng Yingchuan Li Zhen Jiang Chunsheng Wang BingBing Li Wei Jiang |
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| Affiliation: | 1. Department of Anesthesiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, China;2. The first two authors contributed equally to this work.;3. Department of Anesthesiology, Zhongshan Hospital Affiliated to Fudan University, Shanghai 200032, China |
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| Abstract: | Pulmonary hypertension is a group of diseases comprising vascular constriction and obstructive changes of the pulmonary vasculature. Phosphodiesterase type 5 inhibitors, for example, sildenafil, can alleviate vascular remodeling in the monocrotaline pulmonary hypertension model in rats. We investigate the mechanisms of sildenafil on the pulmonary vascular remodeling of pulmonary hypertension induced by monocrotaline (MCT) in rats. Thirty Sprague‐Dawley rats (weighing 200–220 g) were administered with MCT abdominal cavity injection or equivalent volume of normal saline (NS) (which were treated as C group n = 10) to induce pulmonary hypertension model. Fourteen days later, 20 MCT treated rats were randomly fed with sildenafil (25mg/kg/day) or placebo as S, P group (10 rats for each group), respectively. Another 6 weeks later, mean pulmonary artery pressure (mPAP), index of right ventricular hypertrophy (RV/LV+S) of all animals were measured under general anesthesia. Pulmonary tissue was collected to investigate pathological features of pulmonary arteries and to measure protein expression of ERK1/ERK2 and MKP1. After 6 weeks, there were significant elevated mPAP and RV/LV+S in both P and S groups. The ratio of wall thickness to vessel diameter in pulmonary arteries with diameters <200 μm were increased in both P and S groups. But the ratio of wall thickness to vessel diameter was smaller in S group than that in P group. The phosphorylation level of ERK1/ERK2 were elevated in both P and S groups, but the level of phosphorlation ERK1/ERK2 were lower in S group than that in P group. Intriguingly, the expression level of MKP1 was significantly increased in both S and P groups, while it was higher in S group than that in P group. The Sildenafil can decrease mPAP and inhibit the progress of pulmonary vascular remodeling in pulmonary hypertension rats. The ERK‐MAP kinase signaling pathway might play a role during this process. |
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| Keywords: | ERK‐MAP kinase signaling Sildenafil Pulmonary hypertension Pulmonary vascular remodeling |
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