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losartan + HCTZ (Gizaar / Hyzaar / Cozaar plus)

✓ Approved

Merck & Co. · AGTR1 · Small Molecule

What is losartan + HCTZ?

losartan + HCTZ is a small molecule developed by Merck & Co.. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesGizaar, Hyzaar, Cozaar plus
CompanyMerck & Co.
Drug ClassSmall Molecule
Molecular TargetAGTR1, SLC12A3
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Merck & Co.

Mechanism of Action

Molecular Targets

losartan + HCTZ acts on 2 molecular targets:

AGTR1angiotensin II receptor type 1 (HAT1R, AT1)
SLC12A3solute carrier family 12 member 3 (NCCT, NCC)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

losartan + HCTZ is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Vascular disordersHypertension✓ Approved

Related Research Articles

PubMedAdvanced genetics (Hoboken, N.J.)2026-07-17

Genetic Bone Diseases: A Scoping Review of Pathology, Symptoms, Diagnosis, Treatment, and New Horizons.

Jones Colin C, Jayasuriya Ambalangodage C AC

Genetic bone diseases are a rare group of afflictions suffered by the general population. However, their rarity should not diminish research efforts to help patients understand and treat their diseases. This review summarizes the pathology, symptoms, diagnosis, and treatment insight into six well-known genetic bone diseases. Only six bone diseases are included due to the relatively low prevalence of them as whole limiting our scope to ensure accurate information and attention is provided for each disease individually. A literature search of PubMed is conducted, including studies published within the past five years (January 2020-December 2025). Thirty-six studies met inclusion criteria, and no significant risk of bias is identified among the selected articles. Study findings are synthesized into disease overview, clinical and radiographic features, and diagnostic and treatment approaches. Actively developing or novel therapies relevant to each disease are also included. These treatments include: fresolimumab for osteogenesis imperfecta, small interfering ribonucleic acid (RNA) therapy for Osteopetrosis, denosumab for Paget's disease of bone, vosoritide/recifercept/infigratinib for achondroplasia, mesenchymal stem cell therapy for craniosynostosis, and combination losartan and atenolol therapy for Marfan syndrome. These treatments are generally more recently acknowledged in literature and are either actively undergoing research or require further research to determine their efficacy.

PMID 42466325
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PubMedZhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery2026-07-17

[Mechanisms of Piezo1-mediated microglial ferroptosis in inhibiting spinal cord injury repair].

Wang Zesen Z, Huang Jiahui J, Liang Bintao B, Zhou Shishuai S et al.

To investigate the mechanism of the mechanosensitive ion channel Piezo1 in microglial ferroptosis following spinal cord injury (SCI), and to assess the effects of Piezo1 inhibition on ameliorating the injury microenvironment and promoting neurological functional recovery. Primary microglia cells were extracted from neonatal 1-2 days C57BL/6 mice and divided into control group, Yoda1 (Piezo1 agonist) group, and Yoda1+GsMTx4 (Piezo1 inhibitor) group. Live/dead cell staining, reactive oxygen species (ROS) fluorescence staining, 5, 5', 6, 6'-tetrachloro-1, 1', 3, 3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) mitochondrial membrane potential detection, and transmission electron microscopy were utilized to assess microglial ferroptosis and mitochondrial functional characteristics. SPF female C57BL/6 mice aged 6 to 8 weeks were used to detect the expression of Piezo1 at different time points after SCI by Western blot, and the two time points with no significant change and the most significant change in Piezo1 expression after SCI were selected for subsequent experiments. T 8, T 9 SCI models were established by modified Allen's method, and were divided into sham operation group, injury group, and injury+shPiezo1 group (Piezo1-targeted interfering virus AAV-shPiezo1 was injected in situ to knock down the expression of Piezo1 14 days before modeling). Colocalization of Piezo1 with microglial markers purinergic receptor P2Y12 (P2ry12), and the expressions of glutathione peroxidase 4 (GPX4) and acyl coenzyme A synthetase long chain member 4 (ACSL4) were observed by immunofluorescence staining. Basso Mouse Scale (BMS) score was used to assess hindlimb motor function in mice. The level of ROS was detected by dihydroethidium (DHE) staining; the content of malondialdehyde (MDA) was detected by MDA kit; the levels of tumor necrosis factor α (TNF-α) and interleukin 10 (IL-10) were detected by ELISA assay; the pathological morphology of spinal cord was observed by HE staining. In vitro experiments showed that compared with the control group, the Yoda1 group had typical ultrastructural changes of ferroptosis, such as increased microglial cell death, enhanced ROS fluorescence, mitochondrial membrane potential depolarization, mitochondrial shrinkage and mitochondrial cristae breakage (all P<0.05), while the GsMTx4 group could partially reverse the above effects ( P<0.05). In vivo experiments demonstrated that the expression of Piezo1 in spinal cord tissue was up-regulated sequentially after SCI, and reached the peak on the 7th day after SCI ( P<0.05), and it was mainly localized in P2ry12-positive microglia. Compared with the injury group, in the injury+shPiezo1 group, the expression of ferroptosis core protein GPX4 in microglia was increased, the expression of ACSL4 was decreased, the levels of ROS and MDA in spinal cord tissue were decreased ( P<0.05), the level of pro-inflammatory factor TNF-α was decreased, and the level of anti-inflammatory factor IL-10 was increased ( P<0.05). In addition, the BMS score was significantly higher than that of the injury group ( P<0.05) from the 14th day after operation, and the spinal cord tissue structure was relatively well preserved, and the cavity area was reduced. SCI activates the Piezo1 channel in microglia, triggering mitochondrial dysfunction and mediating cellular ferroptosis, thereby aggravating secondary neuroinflammation. Targeted inhibition of Piezo1 effectively blocks the ferroptosis process, ameliorates the immune microenvironment, and promotes tissue repair and locomotor functional recovery after SCI.

PMID 42464547
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PubMedJournal of ethnopharmacology2026-07-17

Chebulinic Acid Suppresses NF-κB/TSLP Signaling Axis via ACLY-Mediated Lipid Metabolism Reprogramming to Ameliorate Atopic Dermatitis.

Wang Mingchan M, Bai Yaxing Y, Guo Yimeng Y, Shen Xin X et al.

Terminalia chebula Retz. (Combretaceae) is a classic medicinal plant in Tibetan medicine, Ayurveda, and Traditional Chinese Medicine. It is traditionally applied to relieve pruritus, erythema and xerosis, which are typical clinical manifestations of atopic dermatitis (AD), and these traditional applications have been scientifically verified. Chebulinic acid (CA), a major phenolic constituent of this plant, inherits its traditional anti-inflammatory and skin-protective potentials. This study aimed to explore the therapeutic potential of CA against AD and clarify its underlying mechanism targeting the lipid metabolism-NF-κB/TSLP axis. FLG-knockout (Flg-/-) mice were divided into six groups to assess skin lesion severity through various measures including ear thickness and histopathology. In vitro, transcriptome and mechanistic analyses were performed in IL-4/IL-13-stimulated HaCaT cells to identify key signaling pathways. Topical CA application significantly ameliorated AD-like symptoms in Flg-/- mice, reducing epidermal thickening, improving lesion scores, enhancing skin barrier function (decreased TEWL), and inhibiting keratinocyte proliferation. CA also reduced serum IgE and TSLP levels, diminished CD4+ T cell infiltration, and downregulated Th2 cytokines (IL-4, IL-5, IL-13) in lesional skin. In vitro, CA suppressed pro-inflammatory mediators (IL-6, IL-8, TSLP) in AD-like keratinocytes. Transcriptomic and pathway analyses revealed that CA targets the ACLY/NF-κB/TSLP axis: CA inhibited ACLY, reducing acetyl-CoA availability, which in turn suppressed NF-κB p65 (RELA) acetylation at K310-critical for TSLP transactivation. This mechanism was validated using the ACLY-specific inhibitor BMS-303141, and further corroborated by genetic ACLY knockdown and acetyl-CoA rescue experiments, which collectively recapitulated CA's inhibitory effects on p65 acetylation and TSLP expression. Our findings demonstrate that CA ameliorates AD by disrupting the ACLY-mediated metabolic-immune loop, linking fatty acid metabolism to NF-κB/TSLP-driven inflammation. This identifies CA as a promising multifaceted therapeutic agent for AD, targeting both barrier dysfunction and immune dysregulation via a novel regulatory axis.

PMID 42462920
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PubMedHypertension research : official journal of the Japanese Society of Hypertension2026-07-16

Urate-lowering effects of losartan: a meta-analysis of randomised controlled trials and target trial emulation.

Xu Xiaoguang X, Naeem Ahlam A, Emmett Amber A, Siedlinski Mateusz M et al.

Common in hypertensive patients, hyperuricaemia is often exacerbated by guideline-recommended antihypertensive therapies such as thiazide diuretics. Losartan is known as an angiotensin II receptor type 1 antagonist with a uricosuric effect, but the magnitude of its efficacy in lowering urate has not been quantified versus a placebo-reference. We sought to quantify the urate-lowering effect of losartan versus placebo using two complementary approaches. We first conducted a meta-analysis of randomised controlled trials (RCTs) to quantify the effect of losartan on serum urate levels versus placebo. We then applied a target trial emulation framework in the UK Biobank as a secondary source of data and a replication experiment. The meta-analysis of six prospective randomised controlled trials (RCTs), including 1119 losartan-treated patients and 1093 controls, demonstrated that losartan reduced serum urate levels by approximately 0.29 mg/dL relative to placebo (95% CI: -0.46 to -0.12, p = 0.0009). In the target trial emulation, 23 losartan-treated individuals showed a reduction in serum urate of approximately 0.35 mg/dL (95% CI: -0.66 to -0.03, p = 0.03) when compared with 92 matched controls, and after accounting for 12 potential confounders including established urate-lowering therapies. Our results provide evidence for a modest yet consistent urate-lowering potential of losartan. This modest biochemical effect (~0.3 mg/dL) may be an attractive option to mitigate the diuretic-induced urate elevation. Thus, losartan can be considered as a favourable antihypertensive choice for patients managed with diuretics or those who are at risk of hyperuricaemia/gout.

PMID 42458015
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PubMedJournal of orthopaedic research : official publication of the Orthopaedic Research Society2026-07-16

An Angiotensin II Receptor Blocker Suppresses Glucose-Induced Oxidative Stress in Human Rotator Cuff-Derived Cells.

Takigami Shunsaku S, Mifune Yutaka Y, Inui Atsuyuki A, Yamaura Kohei K et al.

Rotator cuff tears are among the most common shoulder disorders, and their incidence increases with age. Hyperglycemic conditions are known to enhance oxidative stress and inflammatory signaling in various tissues, potentially contributing to tendon degeneration. Angiotensin II receptor blockers (ARBs) are widely used antihypertensive agents known to possess antioxidant and anti-inflammatory properties. However, their effects on hyperglycemia-induced oxidative stress in tendon tissues remain unclear. This study investigated whether losartan, an ARB, suppresses high glucose-induced oxidative stress in human rotator cuff-derived cells. Tendon-derived cells obtained during arthroscopic rotator cuff repair were cultured and divided into four groups: control (C), control with losartan (CL; 100 μM), high glucose (H; 33 mM), and high glucose with losartan (HL). Cell viability was evaluated using the Cell Counting Kit-8. Expression of RAGE, NOX1, NOX4, IL-6, IL-1β, COL1, and COL3 was analyzed by quantitative real-time PCR. Reactive oxygen species (ROS) were detected by DCFH-DA staining, and apoptosis was assessed by TUNEL staining. High glucose exposure significantly reduced cell viability and increased ROS production and inflammatory gene expression. Losartan treatment under high-glucose conditions mitigated these changes, maintaining cell viability and suppressing the expression of RAGE, NOX1, IL-6, and IL-1β. These findings suggest that losartan modulates oxidative stress pathways under hyperglycemic conditions and may represent a potential therapeutic strategy.

PMID 42458213
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PubMedJournal of oral rehabilitation2026-07-16

Comparative Study of Clinical Characteristics According to Pain Distribution in Lingual Burning Mouth Syndrome.

Sim Yoohyun Y, Ha Na-Yeon NY, Ko Seok-Jae SJ, Park Jae-Woo JW et al.

The pathophysiology of burning mouth syndrome (BMS) remains unclear. To compare the clinical characteristics of patients with lingual BMS according to pain distribution. The medical records of patients with lingual BMS who visited the oral clinic of Kyung Hee University Korean Medicine Hospital between January 2023 and December 2024 were retrospectively reviewed. Patients were classified according to tongue pain distribution as follows: laterality (unilateral vs. bilateral), extent (localised vs. generalised) and central tongue involvement (non-central vs. central involvement). Group differences and associations among clinical characteristics, including pain intensity (visual analog scale [VAS]), quality of life, salivary flow and taste disturbance, were assessed. In total, 256 patients were included. Patients with bilateral pain showed significantly higher pain intensity than those with unilateral pain. Patients with generalised pain reported significantly higher pain intensity than those with localised pain. Patients with central involvement showed significantly higher pain intensity than those with non-central involvement. Pain intensity was negatively associated with quality of life in most subgroups, except the unilateral subgroup. Taste disturbance was associated with clinically significant pain (VAS ≥ 4) in the unilateral and localised subgroups, whereas reduced salivary flow was associated with clinically significant pain in the central involvement subgroup. Pain distribution may help identify clinical subtypes of lingual BMS and support individualised assessment. Herein, pain distribution was associated with differences in pain intensity, quality of life, taste disturbance and salivary flow, underscoring the heterogeneous and multifactorial pathophysiology of lingual BMS and the need for tailored management.

PMID 42457630
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