Mineralocorticoid receptor antagonists attenuate exaggerated exercise pressor reflex responses in hypertensive rats
Mineralocorticoid receptor antagonists attenuate exaggerated exercise pressor reflex responses in hypertensive rats
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DOI：
10.1152/ajpheart.00155.2017
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发表时间：
2017-10-01
影响因子：
4.8
通讯作者：
Smith, Scott A.
中科院分区：
文献类型：
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作者：
Downey, Ryan M.;Mizuno, Masaki;Smith, Scott A.
高血压患者对运动的夸大心率(HR)和血压反应在一定程度上是通过运动加压反射(EPR)的过度活动来调节的。这种EPR功能障碍的机制尚未完全阐明。先前的研究表明，外源性给予醛固酮刺激正常健康大鼠的盐皮质激素受体(MRS)，可复制高血压动物的EPR过度活动特征。相反，本研究的目的是观察螺内酯(SPIR)或依普利酮(EPL)拮抗去脑高血压大鼠MR是否能改善异常的EPR功能。本实验观察了正常血压Wistar-京都大鼠和自发性高血压大鼠(SHR)对EPR或肌肉机械反射(EPR的一种成分)激活所引起的平均动脉压(MAP)和心率的变化。经SPIR或EPL处理后，SHR对EPR(NC：45+/-7 mm Hg，SPIR：26+/-4 mm Hg，EPL：24+/-5 mm Hg，P=0.02)和机械反射(NC：34+/-9 mm Hg，SPIR：17+/-3 mm Hg，EPL：15+/-3 mm Hg，P=0.03)的反应明显减弱。经SPIR或EPL处理的SHR对EPR(NC：17+/-3次/min，SPIR：9+/-1次/min，EPL：9+/-2次/min，P=0.01)和机械反射(NC：15+/-3次/min，SPIR：6+/-1次/min，EPL：7+/-1次/min，P=0.01)的反应也明显减弱。接受SPIR治疗的Wistar-京都大鼠对EPR或机械感受器反射激活的MAP或HR反应没有显著差异。这些数据表明，拮抗MRS可能是治疗高血压患者EPR过度活动的有效策略。值得注意的是，高血压患者对运动的心血管反应与过度活跃的运动加压反射(EPRS)有关。小剂量糖皮质激素受体拮抗剂(螺内酯或依普利酮)可有效改善高血压患者异常的EPR功能。有效地治疗EPR过度活动可能会降低高血压患者与体力活动相关的心血管风险。
Exaggerated heart rate (HR) and blood pressure responses to exercise in hypertension are mediated, in part, by overactivity of the exercise pressor reflex (EPR). The mechanisms underlying this EPR dysfunction have not been fully elucidated. Previous studies have shown that stimulation of mineralocorticoid receptors (MRs) with exogenous administration of aldosterone in normal, healthy rats reproduces the EPR overactivity characteristic of hypertensive animals. Conversely, the purpose of this study was to examine whether antagonizing MR with spironolactone (SPIR) or eplerenone (EPL) in decerebrated hypertensive rats ameliorates abnormal EPR function. Changes in mean arterial pressure (MAP) and HR induced by EPR or muscle mechanoreflex (a component of EPR) activation were assessed in normotensive Wistar-Kyoto rats and spontaneously hypertensive rats (SHRs) fed normal chow (NC) or a customized diet containing either SPIR or EPL for 3 wk. SHRs treated with SPIR or EPL had significantly attenuated MAP responses to EPR (NC: 45 +/- 7 mmHg, SPIR: 26 +/- 4 mmHg, and EPL: 24 +/- 5 mmHg, P = 0.02) and mechanoreflex (NC: 34 +/- 9 mmHg, SPIR: 17 +/- 3 mmHg, and EPL: 15 +/- 3 mmHg, P = 0.03) activation. SHRs treated with SPIR or EPL also showed significantly attenuated HR responses to EPR (NC: 17 +/- 3 beats/min, SPIR: 9 +/- 1 beats/min, and EPL: 9 +/- 2 beats/min, P = 0.01) and mechanoreflex (NC: 15 +/- 3 beats/min, SPIR: 6 +/- 1 beats/min, and EPL: 7 +/- 1 beats/min, P = 0.01) activation. Wistar-Kyoto rats treated with SPIR did not demonstrate significant differences in MAP or HR responses to EPR or mechanoreflex activation. The data suggest that antagonizing MRs may be an effective strategy for the treatment of EPR overactivity in hypertension.NEW & NOTEWORTHY Exaggerated cardiovascular responses to exercise in hypertensive patients are linked with overactive exercise pressor reflexes (EPRs). Administration of low-dose mineralocorticoid receptor antagonists (spironolactone or eplerenone) effectively ameliorates abnormal EPR function in hypertension. Effective treatment of EPR overactivity may reduce the cardiovascular risks associated with physical activity in hypertension.