去肾交感神经支配术治疗难治性高血压（实验性）
肾交感神经激活是原发性高血压病理生理学机制的一部分；有关去肾交感神经术的研究却报道了疗效不一的结果。[115]Bhatt DL, Kandzari DE, O'Neill WW, et al; SYMPLICITY HTN-3 Investigators. A controlled trial of renal denervation for resistant hypertension. N Engl J Med. 2014 Apr 10;370(15):1393-401.https://www.nejm.org/doi/10.1056/NEJMoa1402670?url_ver=Z39.88-2003http://www.ncbi.nlm.nih.gov/pubmed/24678939?tool=bestpractice.com[116]Kandzari DE, Böhm M, Mahfoud F, et al. Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial. Lancet. 2018 Jun 9;391(10137):2346-55.http://www.ncbi.nlm.nih.gov/pubmed/29803589?tool=bestpractice.com[117]Azizi M, Schmieder RE, Mahfoud F, et al. Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicentre, international, single-blind, randomised, sham-controlled trial. Lancet. 2018 Jun 0;391(10137):2335-45.http://www.ncbi.nlm.nih.gov/pubmed/29803590?tool=bestpractice.com[118]Oliveras A, Armario P, Clarà A, et al. Spironolactone versus sympathetic renal denervation to treat true resistant hypertension: results from the DENERVHTA study: a randomized controlled trial. J Hypertens. 2016 Sep;34(9):1863-71.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972478/http://www.ncbi.nlm.nih.gov/pubmed/27327441?tool=bestpractice.com[119]Rosa J, Widimský P, Waldauf P, et al. Role of adding spironolactone and renal denervation in true resistant hypertension: one-year outcomes of randomized PRAGUE-15 study. Hypertension. 2015 Feb;67(2):397-403.https://www.ahajournals.org/doi/full/10.1161/HYPERTENSIONAHA.115.06526http://www.ncbi.nlm.nih.gov/pubmed/26693818?tool=bestpractice.com[120]Fadl Elmula FEM, Feng YM, Jacobs L, et al. Sham or no sham control: that is the question in trials of renal denervation for resistant hypertension: a systematic meta-analysis. Blood Press. 2017 Aug;26(4):195-203.https://www.tandfonline.com/doi/full/10.1080/08037051.2017.1311769http://www.ncbi.nlm.nih.gov/pubmed/28443356?tool=bestpractice.com去肾交感神经术可用于临床试验，尚未被用于日常临床实践中。
压力反射激活疗法
对颈动脉窦的压力感受器反射系统进行电刺激也被称为压力反射激活疗法 (baroreflex activation therapy, BAT)，可能降低难治性高血压患者的血压。电刺激器可直接激活传入压力反射神经，由于技术原因，此前临床试验中激活传入压力反射神经失败。然而，新型可植入型装置可以克服一些以前遇到的技术问题，该装置可刺激颈动脉窦壁，并已在可行性研究中证实可降低血压。[121]Heusser K, Tank J, Engeli S, et al. Carotid baroreceptor stimulation, sympathetic activity, baroreflex function, and blood pressure in hypertensive patients. Hypertension. 2010 Mar;55(3):619-26.http://hyper.ahajournals.org/content/55/3/619.longhttp://www.ncbi.nlm.nih.gov/pubmed/20101001?tool=bestpractice.com[122]Illig KA, Levy M, Sanchez L, et al. An implantable carotid sinus stimulator for drug-resistant hypertension: surgical technique and short-term outcome from the multicenter phase II Rheos feasibility trial. J Vasc Surg. 2006 Dec;44(6):1213-8.http://www.ncbi.nlm.nih.gov/pubmed/17145423?tool=bestpractice.com[123]Scheffers IJ, Kroon AA, Schmidli J, et al. Novel baroreflex activation therapy in resistant hypertension: results of a European multi-center feasibility study. J Am Coll Cardiol. 2010 Oct 5;56(15):1254-8.https://www.sciencedirect.com/science/article/pii/S0735109710027221?via%3Dihubhttp://www.ncbi.nlm.nih.gov/pubmed/20883933?tool=bestpractice.com 在 RheosPivotal 临床试验中，评估了可接受压力反射激活疗法 (BAT) 的难治性高血压患者的长期血压控制情况，在 22 至 53 个月长期随访中，血压下降可维持。[124]Bakris GL, Nadim MK, Haller H, et al. Baroreflex activation therapy provides durable benefit in patients with resistant hypertension: results of long-term follow-up in the Rheos Pivotal Trial. J Am Soc Hypertens. 2012;6:152-158.http://www.ncbi.nlm.nih.gov/pubmed/22341199?tool=bestpractice.com
补充 L-精氨酸
口服补充 L-精氨酸、氨基酸和一氧化氮合酶，已证实可显著降低收缩压和舒张压。[125]Dong JY, Qin LQ, Zhang Z, et al. Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials. Am Heart J. 2011 Dec;162(6):959-65.http://www.ncbi.nlm.nih.gov/pubmed/22137067?tool=bestpractice.com
补充维生素 C
在短期试验中，已证实补充维生素 C 可降低收缩压和舒张压。还需进行长期试验研究以检测补充维生素 C 对血压和临床事件的影响。[126]Juraschek SP, Guallar E, Appel LJ, et al. Effects of vitamin C supplementation on blood pressure: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2012 May;95(5):1079-88.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325833/http://www.ncbi.nlm.nih.gov/pubmed/22492364?tool=bestpractice.com
补充维生素 D
横断面研究数据显示，低水平 25-羟基维生素 D 与较高的收缩压和较高发病率的高血压有关。[127]Tamez H, Thadhani RI. Vitamin D and hypertension: an update and review. Curr Opin Nephrol Hypertens. 2012 Sep;21(5):492-9.http://www.ncbi.nlm.nih.gov/pubmed/22820371?tool=bestpractice.com 大规模观察性研究显示两者之间有一种种较弱、相似的联系。通过对肾素-血管紧张素-醛固酮轴的调节介导，这种效果可视为部分介导。[128]Tamez H, Kalim S, Thadhani RI. Does vitamin D modulate blood pressure? Curr Opin Nephrol Hypertens. 2013 Mar;22(2):204-9.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984388/http://www.ncbi.nlm.nih.gov/pubmed/23299053?tool=bestpractice.com 随机对照试验与观察性数据有冲突，很可能是由于所研究的人群、使用的维生素 D 剂量和未测定的混杂因素存在差异。系统评价发现，在迄今的研究中，维生素 D 补充对降低血压无效。[129]Beveridge LA, Struthers AD, Khan F, et al; D-PRESSURE Collaboration. Effect of vitamin D supplementation on blood pressure: a systematic review and meta-analysis incorporating individual patient data. JAMA Intern Med. 2015 May;175(5):745-54.http://archinte.jamanetwork.com/article.aspx?articleid=2195120http://www.ncbi.nlm.nih.gov/pubmed/25775274?tool=bestpractice.com 在建议使用维生素 D 预防或治疗高血压之前，需要开展大型随机试验，关注存在重度维生素 D 缺乏的高血压患者。
钙补充
初步数据表明，钙摄入的增加会轻微降低血压正常的人的收缩压和舒张压，特别是年轻人。这可能对预防和公共卫生具有一定意义，但需要更多和更大的研究。[130]Cormick G, Ciapponi A, Caffereta ML, et al. Calcium supplementation for prevention of primary hypertension. Cochrane Database Syst Rev. 2015 Jun 30;(6):CD010037.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010037.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/26126003?tool=bestpractice.com
在使用钠-葡萄糖协同转运蛋白 2 (SGLT2) 抑制剂的2 型糖尿病患者中
现已发现钠-葡萄糖协同转运蛋白 2 (sodium-glucose transporter-2, SGLT2) 抑制剂具有治疗高血压的作用。恩格列净是一种降血糖药物（钠-葡萄糖转运蛋白-2 [SGLT-2] 抑制剂），现已发现在长达 2.6 年时间里，恩格列净可降低 2 型糖尿病患者的血压和心血管风险。[131]Tikkanen I, Narko K, Zeller C, et al; EMPA-REG BP Investigators. Empagliflozin reduces blood pressure in patients with type 2 diabetes and hypertension. Diabetes Care. 2015 Mar;38(3):420-8.http://care.diabetesjournals.org/content/38/3/420.longhttp://www.ncbi.nlm.nih.gov/pubmed/25271206?tool=bestpractice.com[132]Zinman B, Wanner C, Lachin JM, et al; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015 Nov 26;373(22):2117-28.http://www.nejm.org/doi/full/10.1056/NEJMoa1504720#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/26378978?tool=bestpractice.com 卡格列净还与具有不同基线血压2型糖尿病患者的血压降低有关。[133]Weir MR, Januszewicz A, Gilbert RE, et al. Effect of canagliflozin on blood pressure and adverse events related to osmotic diuresis and reduced intravascular volume in patients with type 2 diabetes mellitus. J Clin Hypertens (Greenwich). 2014 Dec;16(12):875-82.https://onlinelibrary.wiley.com/doi/full/10.1111/jch.12425http://www.ncbi.nlm.nih.gov/pubmed/25329038?tool=bestpractice.com
阿米洛利
针对难治性高血压的 PATHWAY-2 研究显示，保钾利尿剂阿米洛利的降压作用与螺内酯相当，这提示阿米洛利可能作为治疗难治性高血压的一种可选药物。[134]Williams B, MacDonald TM, Morant SV, et al. Endocrine and haemodynamic changes in resistant hypertension, and blood pressure responses to spironolactone or amiloride: the PATHWAY-2 mechanisms substudies. Lancet Diabetes Endocrinol. 2018 Jun;6(6):464-75.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966620/http://www.ncbi.nlm.nih.gov/pubmed/29655877?tool=bestpractice.com
