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格列净类药物在高血压中的作用:基本机制与临床见解

Gliflozins in hypertension: basic mechanisms and clinical insights.

作者信息

Rieg Timo, Liu Ruisheng, Staruschenko Alexander

机构信息

Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, United States.

Hypertension and Kidney Research Center, University of South Florida, Tampa, Florida, United States.

出版信息

Am J Physiol Renal Physiol. 2025 Jul 1;329(1):F32-F45. doi: 10.1152/ajprenal.00119.2025. Epub 2025 May 27.


DOI:10.1152/ajprenal.00119.2025
PMID:40421752
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12264825/
Abstract

Sodium-glucose cotransport (SGLT) inhibitors, or gliflozins, initially developed for managing type 2 diabetes mellitus, have emerged as promising therapeutic agents for hypertension, offering both cardiovascular and renal protection. Recently, a dual SGLT1/SGLT2 inhibitor was approved for the treatment of heart failure (HF), including preserved and reduced ejection fraction. Clinical trials consistently demonstrate the ability of gliflozins to lower blood pressure (BP) and reduce cardiovascular events, particularly in patients with comorbid conditions such as chronic kidney disease and HF. However, these trials typically include hypertension as a comorbidity rather than as the primary condition, and data specific to patients with hypertension and without diabetes mellitus remain limited. This review highlights recent clinical and basic mechanistic insights into the antihypertensive effects of gliflozins. We discuss their influence on BP regulation, including modulation of renal sodium handling, the renin-angiotensin-aldosterone system, and vascular function. In addition, gliflozins exhibit significant anti-inflammatory and antifibrotic properties, reducing the risk of organ damage associated with chronic hypertension. Their metabolic benefits extend beyond glucose control, contributing to weight loss, and reduced uric acid levels, collectively supporting better cardiovascular outcomes. Accordingly, we also provide a brief overview of these metabolic effects. As ongoing research continues to explore the broader therapeutic applications of gliflozins, these agents may become integral to the management of hypertension, particularly in patients with complex cardiovascular and renal conditions.

摘要

钠-葡萄糖协同转运蛋白(SGLT)抑制剂,即格列净类药物,最初是为治疗2型糖尿病而研发的,现已成为治疗高血压的有前景的治疗药物,具有心血管和肾脏保护作用。最近,一种双重SGLT1/SGLT2抑制剂被批准用于治疗心力衰竭(HF),包括射血分数保留和降低的情况。临床试验一致证明格列净类药物有降低血压(BP)和减少心血管事件的能力,特别是在患有慢性肾病和HF等合并症的患者中。然而,这些试验通常将高血压作为合并症而非主要病症,针对无糖尿病的高血压患者的具体数据仍然有限。本综述重点介绍了近期关于格列净类药物降压作用的临床和基础机制见解。我们讨论了它们对血压调节的影响,包括对肾脏钠处理、肾素-血管紧张素-醛固酮系统和血管功能的调节。此外,格列净类药物具有显著的抗炎和抗纤维化特性,降低了与慢性高血压相关的器官损伤风险。它们的代谢益处不仅限于血糖控制,还有助于体重减轻和尿酸水平降低,共同支持更好的心血管结局。因此,我们也简要概述了这些代谢作用。随着正在进行的研究继续探索格列净类药物更广泛的治疗应用,这些药物可能会成为高血压管理的重要组成部分,特别是在患有复杂心血管和肾脏疾病的患者中。

相似文献

[1]
Gliflozins in hypertension: basic mechanisms and clinical insights.

Am J Physiol Renal Physiol. 2025-7-1

[2]
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[3]
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[4]
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[5]
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Cardiovasc Diabetol. 2025-7-14

[6]
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[7]
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Arch Ital Urol Androl. 2025-6-30

[8]
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Cochrane Database Syst Rev. 2018-6-28

[9]
Blood pressure lowering efficacy of renin inhibitors for primary hypertension.

Cochrane Database Syst Rev. 2017-4-5

[10]
Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular events, death, and major safety outcomes in adults with type 2 diabetes: a systematic review and meta-analysis.

Lancet Diabetes Endocrinol. 2016-3-18

引用本文的文献

[1]
Association Between SGLT2 Inhibitor Therapy and the Incidence of Tinnitus in Patients with Type 2 Diabetes: A Retrospective Cohort Study.

Audiol Res. 2025-8-9

[2]
High-Fructose-Induced Salt-Sensitive Hypertension: The Potential Benefit of SGLT4 or SGLT5 Modulation.

Nutrients. 2025-7-30

本文引用的文献

[1]
Glucose absorption by isolated, vascularly perfused rat intestine: A significant paracellular contribution augmented by SGLT1 inhibition.

Acta Physiol (Oxf). 2025-5

[2]
Dehydration-induced AVP stimulates glucagon release and ketogenesis.

Am J Physiol Endocrinol Metab. 2025-4-1

[3]
2025 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.

Circulation. 2025-2-25

[4]
Recent advances on immunity and hypertension: the new cells on the kidney block.

Am J Physiol Renal Physiol. 2025-3-1

[5]
Effect of empagliflozin on weight in patients with prediabetes and diabetes.

Sci Rep. 2025-1-2

[6]
Effects of Empagliflozin and Dapagliflozin in alleviating cardiac fibrosis through SIRT6-mediated oxidative stress reduction.

Sci Rep. 2024-12-28

[7]
Empagliflozin Attenuates Neointima Formation After Arterial Injury and Inhibits Smooth Muscle Cell Proliferation and Migration by Suppressing Platelet-Derived Growth Factor-Related Signaling.

J Am Heart Assoc. 2024-11-19

[8]
Dapagliflozin mitigates cellular stress and inflammation through PI3K/AKT pathway modulation in cardiomyocytes, aortic endothelial cells, and stem cell-derived β cells.

Cardiovasc Diabetol. 2024-10-29

[9]
Long-Term Effects of Empagliflozin in Patients with Chronic Kidney Disease.

N Engl J Med. 2025-2-20

[10]
Handling the sugar rush: the role of the renal proximal tubule.

Am J Physiol Renal Physiol. 2024-12-1

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