硫酸多糖DPS对肾血管性高血压大鼠的降压作用及其相关机制(英文)

目的:观察硫酸多糖(DPS)对肾血管性高血压大鼠的降压作用并对其机制进行初步探讨。方法:(1)急性降压实验:DPS单次舌下静脉注射给药,给药前后以颈总动脉插管法测定大鼠动脉血压和心率。(2)口服预防给药实验:在肾血管性高血压大鼠造模第二天起口服预防给药五周,每日一次。于给药前、后第三周和第六周分别以大鼠尾动脉测压法测定动脉血压和心率。实验结束前,将大鼠断头取血,测定血清中一氧化氮(NO)的含量;用放射免疫法测定血浆中血管紧张素Ⅱ(Ang Ⅱ)和内皮素-1(ET-1)的含量。血管紧张素转化酶抑制剂卡托普利作为口服预防给药实验阳性对照药。结果:在急性降压实验中,DPS能够显著降低肾血管性高血压大鼠的收缩压和舒张压且其降压强度呈剂量依赖性,降压的同时伴有心率减慢。DPS口服预防给药五周,剂量依赖性抑制大鼠的收缩压和舒张压升高,DPS 50 mg/kg的降压效果与卡托普利14 mg/kg相当。DPS给药五周,可显著增加血清中NO的含量和降低血浆中ET-1的含量;亦降低血浆中Ang Ⅱ的含量。结论:硫酸多糖DPS对肾血管性高血压大鼠具有良好的降压作用。其降压机制可能与其促进体内NO生成或释放、降低ET-1和Ang Ⅱ的含量有关。

Antihypertensive effects of D-polymannuronic sulfate and its related mechanisms in renovascular hypertensive rats

AIM: To investigate the antihypertensive effects of D-polymannuronic sulfate (DPS), a kind of sulfated polysaccharide, and the underlying mechanisms in renovascular hypertensive rats (RHR). METHODS: Used two-kidney one clip (Goldblatt, 2-K 1C) method to produce RHR model. DPS was given i.v. or ig for 5 wk with the initiation of establishment of RHR. Serum nitric oxide (NO) was determined with NO kit; plasma angiotensin II (Ang II) and endothelin-1 (ET-1) were measured by radioimmumoassays. RESULTS: In acute therapeutic experiments, DPS markedly reduced systolic blood pressure (SBP) and diastolic blood pressure (DBP) dose-dependently and decreased heart rate (HR) with reduction in arterial blood pressure. In the prophylactic experiments, DPS prevented the rise in SBP and DBP in a dose-dependent manner. The hypotensive potency of DPS 50 mg/kg is comparable to that of captopril (14 mg/kg). Moreover, DPS elevated serum NO contents and lowered plasma concentrations of Ang II and ET-1. CONCLUSION: The antihypertensive activities of DPS might be involved both in increasing the generation of nitric oxide and in decreasing the production of angiotensin II and endothelin-1 in vivo.