Pitfalls of Therapies Targeting the Nitric Oxide Signaling Pathway in Heart Failure With Preserved Ejection Fraction.

IF 2.5 4区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Journal of Cardiovascular Pharmacology Pub Date : 2026-08-01 Epub Date: 2026-07-20 DOI:10.1097/FJC.0000000000001844

Skylar A Loeb, Darla L Tharp, Scott D Zawieja, Soumiya Pal, Antonio Abbate, Brant E Isakson

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Abstract

Abstract: Over 30 million individuals globally are afflicted with heart failure with preserved ejection fraction (HFpEF). Despite this substantial figure, treatment options for HFpEF remain limited. This is largely attributed to the variability in disease features and comorbidities with which patients present in the clinic. A common feature among patients with HFpEF is reduced nitric oxide (NO) bioavailability-a finding which prompted the use of therapeutics targeting the NO signaling pathway in HFpEF preclinical and clinical trials. Although many of these therapeutics were successful in animal models, clinical trials have yielded neutral, negative, or contradictory results. In this review, we will summarize the outcomes of HFpEF clinical trials investigating drugs that target the NO signaling pathway (nitrates, nitrites, soluble guanylyl cyclase stimulators, and phosphodiesterase 5 inhibitors) and discuss potential pitfalls underlying the neutral or negative results, as well as considerations for the design of future studies.

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针对保留射血分数的心力衰竭的一氧化氮信号通路的治疗陷阱。

全球有超过3000万人患有保留射血分数（HFpEF）心力衰竭。尽管这个数字很大，但HFpEF的治疗选择仍然有限。这在很大程度上归因于患者在临床中出现的疾病特征和合并症的可变性。HFpEF患者的一个共同特征是一氧化氮（NO）生物利用度降低，这一发现促使在HFpEF临床前和临床试验中使用针对NO信号通路的治疗方法。虽然许多治疗方法在动物模型中取得了成功，但临床试验却产生了中性、阴性或相互矛盾的结果。在这篇综述中，我们将总结HFpEF临床试验的结果，研究针对NO信号通路的药物（硝酸盐、亚硝酸盐、可溶性鸟酰环化酶[sGC]刺激剂和磷酸二酯酶5 [PDE5]抑制剂），并讨论中性或阴性结果的潜在缺陷，以及未来研究设计的考虑。

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来源期刊

Journal of Cardiovascular Pharmacology 医学-心血管系统

CiteScore

5.10

自引率

3.30%

发文量

367

审稿时长

1 months

期刊介绍： Journal of Cardiovascular Pharmacology is a peer reviewed, multidisciplinary journal that publishes original articles and pertinent review articles on basic and clinical aspects of cardiovascular pharmacology. The Journal encourages submission in all aspects of cardiovascular pharmacology/medicine including, but not limited to: stroke, kidney disease, lipid disorders, diabetes, systemic and pulmonary hypertension, cancer angiogenesis, neural and hormonal control of the circulation, sepsis, neurodegenerative diseases with a vascular component, cardiac and vascular remodeling, heart failure, angina, anticoagulants/antiplatelet agents, drugs/agents that affect vascular smooth muscle, and arrhythmias. Appropriate subjects include new drug development and evaluation, physiological and pharmacological bases of drug action, metabolism, drug interactions and side effects, application of drugs to gain novel insights into physiology or pathological conditions, clinical results with new and established agents, and novel methods. The focus is on pharmacology in its broadest applications, incorporating not only traditional approaches, but new approaches to the development of pharmacological agents and the prevention and treatment of cardiovascular diseases. Please note that JCVP does not publish work based on biological extracts of mixed and uncertain chemical composition or unknown concentration.