A Combination of Intravenous Genistein Plus Mg2+ Enhances Antihypertensive Effects in SHR by Endothelial Protection and BKCa Channel Inhibition.
A Combination of Intravenous Genistein Plus Mg2+ Enhances Antihypertensive Effects in SHR by Endothelial Protection and BKCa Channel Inhibition.
复制标题
静脉注射金雀异黄素加 Mg2 的组合通过内皮保护和 BKCa 通道抑制增强 SHR 的抗高血压作用。
DOI：
10.1093/ajh/hpv005
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发表时间：
2015-09
影响因子：
3.2
通讯作者：
Liming Zhang
中科院分区：
文献类型：
--
作者：
Xiaoran Wang;Xiaoli Li;Lei Wang;Liming Zhang
背景
在28只12周龄雄性自发性高血压大鼠（SHR）上观察了染料木黄酮（GST）和镁（Mg）合用对高血压形成的影响。实验分为四组：SHR（0.9%NaCl + DMSO）、SHR + GST（0.9%NaCl + GST 5mg/kg/d）、SHR + Mg（Mg（2+）0.75mmol/kg/d + DMSO）和SHR + GST + Mg（Mg（2+）0.75mmol/kg/d + GST 5mg/kg/d）。还包括一组血压正常的遗传对照Wistar-Kyoto（WKY）大鼠进行比较。每天静脉给药30天。
方法
每5天用尾袖容积描记法测量收缩压（SBP）和心率。用等长测力传感器检测肠系膜动脉的血管张力。全细胞膜片钳技术检测大电导钙激活钾通道（BKCa）电流。
结果
SHR的SBP显著高于WKY大鼠。GST或Mg可降低SHR的收缩压。它们的组合增强了抗高血压作用，如显著降低的SBP和更短的起效时间所示。GST或Mg单独改善SHR的内皮功能障碍。然而，它们的组合再次增强了内皮保护，几乎恢复了WKY中所见的最大舒张反应。SHR的BKCa电流较WKY大鼠明显增加。GST、Mg及其组合使BKCa电流恢复到WKY大鼠的水平。
结论
GST和Mg的组合产生抗高血压作用和内皮功能障碍的改善，其显著大于单独使用时的效果。这些结果为预防和治疗高血压及相关心血管疾病提供了一种新的可行方案。
BACKGROUND
The effects of combining genistein (GST) plus magnesium (Mg) upon the development of hypertension were examined in 28 twelve-week-old male spontaneous hypertension rats (SHRs). Four experimental groups were tested: SHR (0.9% NaCl and DMSO), SHR + GST (0.9% NaCl and GST 5mg/kg/day), SHR + Mg (Mg(2+) 0.75 mmol/kg/day and DMSO), and SHR + GST + Mg (Mg(2+) 0.75 mmol/kg/day and GST 5mg/kg/day). A group of normotensive genetic control, Wistar-Kyoto (WKY) rats were also included for comparison. Drugs were administrated intravenously daily for 30 days.
METHODS
Systolic blood pressure (SBP) and heart rate were measured by tail-cuff plethysmography every five days. Vascular tone of mesenteric arteries was examined by an isometric force transducer. Big-conductance calcium-activated potassium channel (BKCa) currents were detected by whole-cell patch-clamp techniques.
RESULTS
SBP in SHRs was significantly elevated vs. that in WKY rats. GST or Mg lowered SBP of SHRs. Their combination enhanced antihypertensive effects, as indicated by significantly lowered SBP and shorter onset times. GST or Mg individually improved endothelial dysfunction of SHRs. However, again their combination enhanced endothelial protection, nearly restoring maximal relaxation responses to those seen in WKY. BKCa currents in SHRs were increased compared with WKY rats. GST, Mg, and their combination restored BKCa currents to those of WKY rats.
CONCLUSIONS
The combination of GST and Mg produces antihypertensive effects and improvement of endothelial dysfunction, which are substantially greater than that when either is used individually. These results suggest a novel and feasible protocol for the prevention and treatment of hypertension and related cardio- and cerebro-vascular diseases.
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影响因子：
3.2
作者：
K. Kisters;F. Wessels;E. Krefting;B. Gremmler;M. Q. Nguyen;J. Kozianka;P. Franitza;F. Tokmak;M. Hausberg
通讯作者：
K. Kisters;F. Wessels;E. Krefting;B. Gremmler;M. Q. Nguyen;J. Kozianka;P. Franitza;F. Tokmak;M. Hausberg
DOI：
10.4196/kjpp.2014.18.1.1
发表时间：
2014-02
期刊：
The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology
影响因子：
--
作者：
Singh VP;Bali A;Singh N;Jaggi AS
通讯作者：
Jaggi AS
影响因子：
3.2
作者：
R. Vilskersts;J. Kuka;E. Liepinsh;H. Cirule;A. Gulbe;I. Kalvinsh;M. Dambrova
通讯作者：
R. Vilskersts;J. Kuka;E. Liepinsh;H. Cirule;A. Gulbe;I. Kalvinsh;M. Dambrova
影响因子：
5.8
作者：
Atteritano, Marco;Marini, Herbert;Squadrito, Francesco
通讯作者：
Squadrito, Francesco
影响因子：
5
作者：
A. Zerrouk;M. Auguet;H. Dabire;A. Brisac;M. Safar;P. Chabrier
通讯作者：
A. Zerrouk;M. Auguet;H. Dabire;A. Brisac;M. Safar;P. Chabrier