Effect Of Propranolol And Phentolamine In Neurogenic Pulmonary Edema

Background:Neurogenic pulmonary edema (NPE) is usually defined as an acute pulmonary edema occurring shortly after a central neurologic insult. It often presents without pre-existing cardiovascular or pulmonary pathology that could explain the edema. It is the most serious complication of hand, foot and mouth disease (HFMD), and its mortality is near to 90% without proper treatment.Alpha adrenergic blocker phentolamine and beta adrenergic blocker propranolol are widely used in the treatment of HFMD nowadays, but the reliability and mechanisams are still unclear. Neuropeptide Y (NPY) and substance P (SP) are important participants in neurogenic inflammation, which is a crucial mechanisam in NPE. Therefore this study aims at studying the effects of phentolamine and propranolol though observing their impact on the secreation of NPY and SP, and providing a theoretical basis for clinic prevention and treatment.Objective:To investigate the effect of propranolol and phentolamine on neurogenic pulmonary edema(NPE).Methods:One hundred and twenty male Wistar rats with body weight of 350g-450g were randomly divided into 4 groups:the control group (group A), the neurogenic pulmonary edema group (group B), the propranolol treatment group (group C) and the phentolamine treatment group (group D) (30 in each group). Diffuse brain injury was induced in the latter three groups. The lung wet/dry ratio was calculated. HE staining was used to measure the histological changes of lung tissues. The levels of neuropeptide Y (NPY) and substance P (SP) in serum and bronchoalveolar lavage fluid(BALF) were detected by enzyme-linked immunosorbent assay (ELISA).The expression of NPY and SP in lung tissues was demonstrated by immunohistochemical staining, and immunohistochemical scores (IHS) was measured after scarifying the animals at different time points (0.5,6 and 24h after injury).Results:In Group B, compared with Group A, water volume in lungs increased at 24h (P<0.05). NPY content in serum was elevated at 6h, while that in BALF was elevated at 6h and 24h (all P＜ 0.05). SP content in serum was elevated at 0.5h and 6h (all P＜0.05), while that in BALF was elevated at 0.5h (P<0.05). The expression of NPY protein in the lung tissue increased at 0.5h,6h and 24h (all P＜0.05), while the levels of SP protein increased at 0.5h (P＜0.05). In group C, compared with group B, water volume in lungs was higher at 6h and 24h (P＜0.05). NPY concentrations in serum were higher at 6h and 24h (all P＜0.05), while those in BALF were higher at 0.5h,6h, and 24h (all P＜0.05). SP concentrations in serum and BALF were higher at 0.5h (all P＜0.05). The expression of NPY protein increased at 6h (P＜0.05), while the levels of SP protein increased at 0.5h,6h and 24h(all P＜0.05).In group D, compare with Group B, the level of NPY in serum was lower at 6h, and that in BALF was lower at 6h and 24h (all P＜0.05). The level of SP in serum was lower at 0.5h compared with group B (P＜0.05).The expression of NPY protein decreased at 6h and 24h (all P＜0.05), while the levels of SP protein decreased at 0.5h (P＜0.05).Conclusions:Phentolamine is effective in reducing NPE through reduction of NPY and SP, while propranolol can stimulate the release of NPY and SP to aggravate NPE following traumatic brain injury in rats.