Q. Fu: UT Southwestern Medical Center, Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, 7232 Greenville Avenue, Suite 435, Dallas, TX 75231, USA.
J Physiol. 2013 Dec 1;591(23):5913-22. doi: 10.1113/jphysiol.2013.261362. Epub 2013 Sep 23.
Cardiovascular risk remains high in patients with hypertension even with adequate blood pressure (BP) control. One possible mechanism may be sympathetic activation via the baroreflex. We tested the hypothesis that chronic inhibition of renin reduces BP without sympathetic activation, but diuresis augments sympathetic activity in elderly hypertensives. Fourteen patients with stage-I hypertension (66 ± 5 (SD) years) were treated with a direct renin inhibitor, aliskiren (n = 7), or a diuretic, hydrochlorothiazide (n = 7), for 6 months. Muscle sympathetic nerve activity (MSNA), BP, direct renin and aldosterone were measured during supine and a graded head-up tilt (HUT; 5 min 30° and 20 min 60°), before and after treatment. Sympathetic baroreflex sensitivity (BRS) was assessed. Both groups had similar BP reductions after treatment (all P < 0.01), while MSNA responses were different between hydrochlorothiazide and aliskiren (P = 0.006 pre/post × drug). Both supine and upright MSNA became greater after hydrochlorothiazide treatment (supine, 72 ± 18 post vs. 64 ± 15 bursts (100 beats)(-1) pre; 60° HUT, 83 ± 10 vs. 78 ± 13 bursts (100 beats)(-1); P = 0.002). After aliskiren treatment, supine MSNA remained unchanged (69 ± 13 vs. 64 ± 8 bursts (100 beats)(-1)), but upright MSNA was lower (74 ± 15 vs. 85 ± 10 bursts (100 beats)(-1); P = 0.012 for pre/post × posture). Direct renin was greater after both treatments (both P < 0.05), while upright aldosterone was greater after hydrochlorothiazide only (P = 0.002). The change in upright MSNA by the treatment was correlated with the change of aldosterone (r = 0.74, P = 0.002). Upright sympathetic BRS remained unchanged after either treatment. Thus, chronic renin inhibition may reduce upright MSNA through suppressed renin activity, while diuresis may evoke sympathetic activation via the upregulated renin-angiotensin-aldosterone system, without changing intrinsic sympathetic baroreflex function in elderly hypertensive patients.
心血管风险在高血压患者中仍然很高，即使血压（BP）得到了充分控制。一种可能的机制可能是通过压力反射的交感神经激活。我们测试了这样一个假设，即慢性抑制肾素会降低血压而不会引起交感神经激活，但利尿剂会增加老年高血压患者的交感神经活性。14 名患有一期高血压的患者（66 ± 5（SD）岁）接受直接肾素抑制剂阿利克仑（n = 7）或利尿剂氢氯噻嗪（n = 7）治疗 6 个月。在仰卧位和分级头高位倾斜（HUT；5 分钟 30°和 20 分钟 60°）期间测量肌肉交感神经活动（MSNA）、BP、直接肾素和醛固酮，在治疗前后进行。评估了交感神经反射敏感性（BRS）。两组治疗后血压均有相似的降低（均 P < 0.01），而氢氯噻嗪和阿利克仑的 MSNA 反应不同（P = 0.006 预/ post × drug）。仰卧位和直立位 MSNA 在氢氯噻嗪治疗后均增加（仰卧位，72 ± 18 post vs. 64 ± 15 次（100 次）（-1）pre；60° HUT，83 ± 10 vs. 78 ± 13 次（100 次）（-1）；P = 0.002）。阿利克仑治疗后，仰卧位 MSNA 保持不变（69 ± 13 vs. 64 ± 8 次（100 次）（-1）），但直立位 MSNA 降低（74 ± 15 vs. 85 ± 10 次（100 次）（-1）；P = 0.012 预/ post × posture）。两种治疗后直接肾素均增加（均 P < 0.05），而仅氢氯噻嗪治疗后直立位醛固酮增加（P = 0.002）。治疗后直立 MSNA 的变化与醛固酮的变化相关（r = 0.74，P = 0.002）。两种治疗后直立位交感神经 BRS 均保持不变。因此，慢性肾素抑制可能通过抑制肾素活性降低直立位 MSNA，而利尿剂可能通过上调肾素-血管紧张素-醛固酮系统引起交感神经激活，而不改变老年高血压患者的固有交感神经反射功能。
