Removal mechanism of Pb(ii) from soil by biochar-supported nanoscale zero-valent iron composite materials.

As an adsorbent, biochar has a highly porous structure and strong adsorption capacity, and can effectively purify the environment. In response to the increasingly serious problem of heavy metal pollution in water, this study used nano zero valent iron and rice husk biochar to prepare a new type of magnetic sheet-like biochar loaded nano zero valent iron (BC-nZVI) composite material through rheological phase reaction, showing remarkable advantages such as low cost, easy preparation, and superior environmental remediation effect. The physical and chemical properties and structure of the material were extensively characterized using various methods such as HRTEM, XPS, FESEM, EDS, XRD, FTIR, and RAMAN. Concurrently, batch experiments were undertaken to assess the removal efficiency of Pb(ii) by BC-nZVI, with investigations into the influence of pH value, temperature, soil water ratio, and initial concentration of heavy metal ion solution on its removal efficiency. The results indicate that the removal of Pb(ii) by BC-nZVI reaches an equilibrium state after around 120 minutes. Under the conditions of pH 6, temperature 20 °C, soil water ratio 1 : 5, and BC-nZVI dosage of 1 g L-1, BC-nZVI can reduce the Pb(ii) content in wastewater with an initial concentration of 30 mg L-1 to trace levels, and the treatment time is about 120 minutes. The analysis of adsorption kinetics and isotherms indicates that the adsorption process of Pb(ii) by BC-nZVI adheres to the quasi-second-order kinetic model and Langmuir model, suggesting a chemical adsorption process. Thermodynamic findings reveal that the adsorption of Pb(ii) by BC-nZVI is spontaneous. Furthermore, BC-nZVI primarily accumulates Pb(ii) through adsorption co-precipitation. BC-nZVI serves as an eco-friendly, cost-effective, and highly efficient adsorbent, showing promising capabilities in mitigating Pb(ii) heavy metal pollution. Its recoverability and reusability facilitated by an external magnetic field make it advantageous for remediating and treating lead-contaminated sites.

Complement factor C1q mediates vascular endothelial dysfunction in STZ-induced diabetic mice.

Diabetes is a significant global public health issue with implications for vascular endothelial cells (ECs) dysfunction and the subsequent development and advancement of diabetic complications. This study aims to compare the cellular and molecular properties of the aorta in normal and streptozotocin (STZ)-induced diabetic mice, with a focus on elucidating potential mechanism underlying EC dysfunction. Here, we performed a single-cell RNA sequencing survey of 32,573 cells from the aorta of normal and STZ-induced diabetic mice. We found a compendium of 10 distinct cell types, mainly ECs, smooth muscle cells (SMCs), fibroblast, pericyte, immune cells and stromal cells. As the diabetes condition progressed, we observed a subpopulation of aortic ECs that exhibited significantly elevated expression of complement (C) molecule C1qa compared to their healthy counterparts. This increased expression of C1qa was found to induce reactive oxygen species (ROS) production, facilitate EC migration and increased permeability, and impair the vasodilation within the aortic segment of mice. Furthermore, AAV-Tie2-shRNA-C1qa was administered into diabetic mice by tail vein injection, showing that inhibition of C1qa in the endothelium led to a reduction in ROS production, decreased vascular permeability, and improved vasodilation. Collectively, these findings highlight the crucial involvement of C1qa in endothelial dysfunction associated with diabetes.

Single-Cell RNA-Seq Reveals Coronary Heterogeneity and Identifies CD133+TRPV4high Endothelial Subpopulation in Regulating Flow-Induced Vascular Tone in Mice.

BACKGROUND: Single-cell RNA-Seq analysis can determine the heterogeneity of cells between different tissues at a single-cell level. Coronary artery endothelial cells (ECs) are important to coronary blood flow. However, little is known about the heterogeneity of coronary artery ECs, and cellular identity responses to flow. Identifying endothelial subpopulations will contribute to the precise localization of vascular endothelial subpopulations, thus enabling the precision of vascular injury treatment. METHODS: Here, we performed a single-cell RNA sequencing of 31 962 cells and functional assays of 3 branches of the coronary arteries (right coronary artery/circumflex left coronary artery/anterior descending left coronary artery) in wild-type mice. RESULTS: We found a compendium of 7 distinct cell types in mouse coronary arteries, mainly ECs, granulocytes, cardiac myocytes, smooth muscle cells, lymphocytes, myeloid cells, and fibroblast cells, and showed spatial heterogeneity between arterial branches. Furthermore, we revealed a subpopulation of coronary artery ECs, CD133+TRPV4high ECs. TRPV4 (transient receptor potential vanilloid 4) in CD133+TRPV4high ECs is important for regulating vasodilation and coronary blood flow. CONCLUSIONS: Our study elucidates the nature and range of coronary arterial cell diversity and highlights the importance of coronary CD133+TRPV4high ECs in regulating coronary vascular tone.

Cost-effective core@shell structured zero-valent iron nanoparticles @ magnetic (nZVI@Fe3O4) for Cr(vi) removal from aqueous solutions: preparation by disproportionation of Fe(ii).

Nanoscale zero-valent iron (nZVI) and its composites are known for their excellent ability to remove Cr(vi), but their preparation can be expensive due to the reduction processes. This study presents a cost-effective method to prepare core@shell structured nZVI@Fe3O4 nanocomposites using a novel Fe(ii) disproportionation reaction. The nZVI@Fe3O4 was thoroughly characterized using various techniques, including FESEM, HRTEM, EDS, XPS, XRD, FTIR, and VSM. Batch experiments were performed to evaluate the removal efficiency of nZVI@Fe3O4 in eliminating Cr(vi) ions from aqueous solutions, while classical models were employed to investigate the influencing factors associated with the removal process. The results showed that a 0.7 mg per ml NaOH solution reacted with Fe(ii) at 150 °C for 0.5 h could be used to prepare nZVI@Fe3O4 composites efficiently and inexpensively. nZVI@Fe3O4 was able to remove more than 99% of Cr(vi) from both simulated Cr(vi) solutions and real electroplating wastewater, and the recovery and preparation could be easily performed using external magnets to separate it from the solution. At pH 6.0, the maximum adsorption capacity (qmax) for Cr(vi) reached 58.67 mg g-1. The reaction mechanism was discussed from the perspective of electron transfer. Overall, the results suggest that nZVI@Fe3O4, an efficient adsorbent prepared using an environmentally friendly and inexpensive Fe(ii) disproportionation reaction, is a promising option for the treatment of Cr(vi) from industrial wastewater and other contaminated water sources.

Functional role of coupling the endothelial TRPV4 and KCa 3.1 channels in regulating coronary vascular tone.

BACKGROUND AND PURPOSE: High-fat diet (HFD) induces dysregulated pathways in coronary artery endothelial cells (CAECs), which leads to altered regulation of vascular tone, tissue perfusion and increases the risk of coronary artery diseases. Ca2+ -activated K+ (KCa ) channels are known to be associated with transient receptor potential (TRP) channels, which are important for regulating endothelial function. But how TRPV4 channels interacts with KCa channels in regulating coronary vascular tone in HFD mice requires further exploration. EXPERIMENTAL APPROACH: TRPV4 channel activity was assessed by fluorescent Ca2+ imaging. Interactions between TRPV4 and KCa 3.1 channels were verified by co-immunoprecipitation and immunofluorescence resonance energy transfer (FRET), and their binding site was found by site-directed mutagenesis. Endothelium-specific TRPV4 knockout (TRPV4EC -/- ) mice were used to study the effect of the interactions between TRPV4-KCa 3.1 channels on coronary vascular tone. Coronary blood flow was measured by Doppler ultrasound device. KEY RESULTS: TRPV4 channels were involved in regulating coronary vascular tone, through coupling with a Ca2+ -sensitive K+ channel (KCa 3.1) in CAECs, affecting vasodilation and coronary blood flow. In mice fed a HFD diet, the coupling was damaged by a high concentration of plasma 1-heptadecanoyl-2-hydroxy-sn-glycero-3-phosphocholine. Using a bridging approach, we then identified folic acid as an effective drug to repair the uncoupled TRPV4-KCa 3.1 channels and to improve coronary arterial function. CONCLUSION AND IMPLICATIONS: Our data highlight the importance of coupling between TRPV4 and KCa 3.1 channels in the regulation of coronary vascular tone and provide a novel strategy for developing new drugs to reduce the incidence of cardiovascular events.

Different Concentrations of Albumin Versus Crystalloid in Patients with Sepsis and Septic Shock: A Meta-Analysis of Randomized Clinical Trials.

OBJECTIVE: The best type of resuscitation fluids for sepsis and septic shock patients remains unclear. The aim of this study was to evaluate the efficacy of different concentrations of albumin on reducing the mortality rate of theses patients by meta-analysis. MATERIALS AND METHODS: PubMed, EMBASE, and Web of Science databases were used for screening the relevant studies. Randomized controlled trials (RCTs) were eligible if they compared the effects of albumin with crystalloid on mortality in patients with sepsis and septic shock. Data were examined and extracted by two reviewers independently. Any disagreements were resolved by consensus with or without the help from a third reviewer. Data including mortality, sample size of the patients, and resuscitation endpoints were extracted. Meta-analysis was carried based on the corresponding odds ratios with 95% confidence intervals. RESULTS: Eight studies with a total of 5124 septic patients and 3482 septic shock patients were included in this study. Compared with crystalloid, the use of albumin may represent a trend toward reduced the 90-day mortality of septic patients (OR 0.91 [0.80, 1.02]; P = .11) and significantly improved the outcome of septic shock patients (OR 0.85 [0.74, 0.99]; P = .04). Further analysis showed a potentially beneficial role of both 4% to 5% and 20% albumin on reducing the mortality of septic patients. The use of 20% albumin significantly decreased the 90-day mortality of septic shock patients (OR 0.81 [0.67, 0.98]; P = .03), which was better than 4% to 5% albumin and crystalloid. CONCLUSIONS: Albumin treatment, particularly 20% albumin, significantly reduced the 90-day mortality in septic shock patients. Both 4% to 5% and 20% of albumin may work better than crystalloid in improving the survival rate of patients with sepsis, but more relative RCTs are required for validation.

Erratum: A Long Non-coding RNA Lnc712 Regulates Breast Cancer Cell Proliferation: Erratum.

[This corrects the article DOI: 10.7150/ijbs.36429.].

Physiological levels of fluid shear stress modulate vascular function through TRPV4 sparklets.

Endothelial calcium (Ca 2+) signaling plays a major role in regulating vasodilation in response to fluid shear stress (FSS) generated by blood flow. Local Ca 2+ influx through single transient receptor potential channel subfamily V member 4 (TRPV4) (termed "sparklets") activated by low concentrations of chemical and biological stimuli has been revealed to modulate vascular function. However, the range in which FSS can initiate TRPV4 sparklets to induce vasodilation is unknown. Here, we assess the activity of TPRV4 sparklets induced by various physiological levels of FSS and investigate the mechanisms involving these Ca 2+ signals in FSS-induced vasodilation. Intact small mesenteric arteries are used for Ca 2+ imaging with a GCaMP2(TRPV4-KO) mouse model and high-speed confocal systems. Markedly increased local Ca 2+ signals are observed in the endothelium under 4-8 dyne/cm 2 FSS, whereas FSS >8 dyne/cm 2 causes global Ca 2+ influx. Further analysis shows that TRPV4 channels form a four-channel group to mediate Ca 2+ sparklets under certain levels of FSS. The large Ca 2+ influx hyperpolarizes endothelial cells by stimulating intermediate (IK)- and small (SK)-conductance Ca 2+-sensitive potassium channels, leading to hyperpolarization of the surrounding smooth muscle cells and ultimately causing endothelium-dependent vasodilation. In conclusion, Ca 2+ influx transits through a small number of endothelial TRPV4 channels opened by certain levels of FSS, which activates the Ca 2+-sensitive IK and SK channels to cause vasodilation.

Endothelial TRPV4-eNOS coupling as a vital therapy target for treatment of hypertension.

BACKGROUND AND PURPOSE: Reduced NO levels and activity are signs of endothelial dysfunction, which is important in mediating BP changes. Previously, we demonstrated that transient receptor potential channel V4 (TRPV4) could form a functional complex with other proteins to mediate vasodilation in endothelial cells (ECs). But how TRPV4 interacts with the NO pathway in larger arteries requires further exploration. EXPERIMENTAL APPROACH: We used single-cell RNA-sequencing to find the CD106+ TRPV4high NOS3high ECs. The TRPV4-eNOS interaction was verified by co-immunoprecipitation and immuno-FRET, and their binding site was found by site-directed mutagenesis. Endothelium-specific TRPV4 knockout (TRPV4EC-/- ) mice were used to study the effect of the TRPV4-eNOS interaction on BP. A small molecule, JNc-463, was designed through molecular docking technology. KEY RESULTS: We uncovered CD106+ TRPV4high NOS3high ECs in the mouse aorta, which could regulate vasodilation via a TRPV4-eNOS interaction, and were essential to regulate BP. The TRPV4-eNOS interaction markedly decreased during the process of hypertension. We further attempted to identify molecules involved in the TRPV4-eNOS interaction and developed a small-molecule drug, JNc-463, which could increase the TRPV4-eNOS interaction to enhance vasodilation and exert antihypertensive effects in mice. CONCLUSION AND IMPLICATIONS: This is the first study integrating single-cell RNA-Seq, single-cell functional study and drug screening in aorta. We identified a subpopulation of CD106+ TRPV4high NOS3high ECs, in which an impaired TRPV4-eNOS interaction was important in the progress of hypertension, and we designed a small molecule, JNc-463, to improve the impaired TRPV4-eNOS interaction in hypertension.

Single-cell analysis of salt-induced hypertensive mouse aortae reveals cellular heterogeneity and state changes.

Elevated blood pressure caused by excessive salt intake is common and associated with cardiovascular diseases in most countries. However, the composition and responses of vascular cells in the progression of hypertension have not been systematically described. We performed single-cell RNA sequencing on the aortic arch from C57BL/6J mice fed a chow/high-salt diet. We identified 19 distinct cell populations representing 12 lineages, including smooth muscle cells (SMCs), fibroblasts, endothelial cells (ECs), B cells, and T cells. During the progression of hypertension, the proportion of three SMC subpopulations, two EC subpopulations, and T cells increased. In two EC clusters, the expression of reactive oxygen species-related enzymes, collagen and contractility genes was upregulated. Gene set enrichment analysis showed that three SMC subsets underwent endothelial-to-mesenchymal transition. We also constructed intercellular networks and found more frequent cell communication among aortic cells in hypertension and that some signaling pathways were activated during hypertension. Finally, joint public genome-wide association study data and our single-cell RNA-sequencing data showed the expression of hypertension susceptibility genes in ECs, SMCs, and fibroblasts and revealed 21 genes involved in the initiation and development of high-salt-induced hypertension. In conclusion, our data illustrate the transcriptional landscape of vascular cells in the aorta associated with hypertension and reveal dramatic changes in cell composition and intercellular communication during the progression of hypertension.

Single-cell transcriptome analysis reveals cellular heterogeneity in the ascending aortas of normal and high-fat diet-fed mice.

The aorta contains numerous cell types that contribute to vascular inflammation and thus the progression of aortic diseases. However, the heterogeneity and cellular composition of the ascending aorta in the setting of a high-fat diet (HFD) have not been fully assessed. We performed single-cell RNA sequencing on ascending aortas from mice fed a normal diet and mice fed a HFD. Unsupervised cluster analysis of the transcriptional profiles from 24,001 aortic cells identified 27 clusters representing 10 cell types: endothelial cells (ECs), fibroblasts, vascular smooth muscle cells (SMCs), immune cells (B cells, T cells, macrophages, and dendritic cells), mesothelial cells, pericytes, and neural cells. After HFD intake, subpopulations of endothelial cells with lipid transport and angiogenesis capacity and extensive expression of contractile genes were defined. In the HFD group, three major SMC subpopulations showed increased expression of extracellular matrix-degradation genes, and a synthetic SMC subcluster was proportionally increased. This increase was accompanied by upregulation of proinflammatory genes. Under HFD conditions, aortic-resident macrophage numbers were increased, and blood-derived macrophages showed the strongest expression of proinflammatory cytokines. Our study elucidates the nature and range of the cellular composition of the ascending aorta and increases understanding of the development and progression of aortic inflammatory disease.

Puerarin induces mouse mesenteric vasodilation and ameliorates hypertension involving endothelial TRPV4 channels.

Puerarin (Pue) is an isoflavone derived from the root of Pueraria lobata, which has been widely used as food and a herb for treating cardiovascular and cerebrovascular diseases. Transient receptor potential vanilloid 4 (TRPV4), a Ca2+-permeable channel with multiple modes of activation, plays an important role in vascular endothelial function and vasodilation. However, no reports have shown the effects of Pue on TRPV4 channels and mouse small mesenteric arteries. In the present study, we performed a molecular docking assay by using Discovery Studio 3.5 software to predict the binding of Pue to TRPV4 protein. The activation of TRPV4 by Pue was determined by intracellular Ca2+ concentration ([Ca2+]i), live-cell fluorescent Ca2+ imaging and patch clamp assays. Molecular docking results indicated a high possibility of Pue-TPRV4 binding. [Ca2+]i and Ca2+ imaging assays showed that Pue activated TRPV4 channels and increased [Ca2+]i in TRPV4-overexpressing HEK293 (TRPV4-HEK293) cells and primary mouse mesenteric artery endothelial cells (MAECs). Patch clamp assay demonstrated that Pue stimulated the TRPV4-mediated cation currents. Additionally, Pue relaxed mouse mesenteric arteries involving the TRPV4-small-conductance Ca2+-activated K+ channel (SKCa)/intermediate-conductance Ca2+-activated K+ channel (IKCa) pathway, and reduced systolic blood pressure (SBP) in high-salt-induced hypertensive mice. Our study found for the first time that Pue acts as a TRPV4 agonist, induces endothelium-dependent vasodilation in mouse mesenteric arteries, and attenuates blood pressure in high-salt-induced hypertensive mice, highlighting the beneficial effect of Pue in treating endothelial dysfunction-related cardiovascular diseases.

TRPC1 participates in the HSV-1 infection process by facilitating viral entry.

Mammalian transient receptor potential (TRP) channels are major components of Ca2+ signaling pathways and control a diversity of physiological functions. Here, we report a specific role for TRPC1 in the entry of herpes simplex virus type 1 (HSV-1) into cells. HSV-1-induced Ca2+ release and entry were dependent on Orai1, STIM1, and TRPC1. Inhibition of Ca2+ entry or knockdown of these proteins attenuated viral entry and infection. HSV-1 glycoprotein D interacted with the third ectodomain of TRPC1, and this interaction facilitated viral entry. Knockout of TRPC1 attenuated HSV-1-induced ocular abnormality and morbidity in vivo in TRPC1-/- mice. There was a strong correlation between HSV-1 infection and plasma membrane localization of TRPC1 in epithelial cells within oral lesions in buccal biopsies from HSV-1-infected patients. Together, our findings demonstrate a critical role for TRPC1 in HSV-1 infection and suggest the channel as a potential target for anti-HSV therapy.

Menthol relieves acid reflux inflammation by regulating TRPV1 in esophageal epithelial cells.

Transient receptor potential cation channel subfamily V member 1 (TRPV1) plays an important role in pain and inflammatory responses. Previous studies have shown that the expression of TRPV1 increases in the sensory neurons of the esophagus during the development of gastroesophageal reflux disease and esophagitis, but the response of TRPV1 in esophageal epithelial cells (EECs), which directly confront the refluxed acid, is still unknown. Here, we found that acid reflux triggered esophageal damage, which was accompanied by increased expression of TRPV1 in EECs and TRPV1 channel activity in these cells. Furthermore, menthol inhibited the Ca2+ influx induced by acid stimulation in EECs. After menthol treatment, the expression of TRPV1 in EECs was significantly reduced, and their hyperplasia was significantly reduced; finally, the inflammation pathway elicited in EECs was diminished in mice with acid reflux. These results suggest that menthol improves the clinical symptoms caused by gastroesophageal acid reflux by interfering with TRPV1 in EECs.

A Long Non-coding RNA Lnc712 Regulates Breast Cancer Cell Proliferation.

Great quantity of intergenic noncoding RNAs (lncRNAs) have been identified in the mammalian genome and involved in various biological processes, especially in the development and metastasis of cancer. In this study, we identified one lncRNA, lncRNA NONHSAT028712 (Lnc712), was highly expressed in breast cancer cell lines and tissues based on microarray screening. Knockdown of Lnc712 largely inhibited breast cancer cell proliferation. Mechanistically, Lnc712 bound specifically to heat-shock protein 90 (HSP90). Interaction between Lnc712 and HSP90 is required for HSP90 binding to cell division cycle 37 (Cdc37). The Lnc712/HSP90/Cdc37 complex regulated cyclin-dependent kinase 2 (CDK2) activation and then triggered breast cancer cell proliferation. In summary, our results identified a new lncRNA regulate breast cancer proliferation though interaction with HSP90.

Aortic heterogeneity across segments and under high fat/salt/glucose conditions at the single-cell level.

The aorta, with ascending, arch, thoracic and abdominal segments, responds to the heartbeat, senses metabolites and distributes blood to all parts of the body. However, the heterogeneity across aortic segments and how metabolic pathologies change it are not known. Here, a total of 216 612 individual cells from the ascending aorta, aortic arch, and thoracic and abdominal segments of mouse aortas under normal conditions or with high blood glucose levels, high dietary salt, or high fat intake were profiled using single-cell RNA sequencing. We generated a compendium of 10 distinct cell types, mainly endothelial (EC), smooth muscle (SMC), stromal and immune cells. The distributions of the different cells and their intercommunication were influenced by the hemodynamic microenvironment across anatomical segments, and the spatial heterogeneity of ECs and SMCs may contribute to differential vascular dilation and constriction that were measured by wire myography. Importantly, the composition of aortic cells, their gene expression profiles and their regulatory intercellular networks broadly changed in response to high fat/salt/glucose conditions. Notably, the abdominal aorta showed the most dramatic changes in cellular composition, particularly involving ECs, fibroblasts and myeloid cells with cardiovascular risk factor-related regulons and gene expression networks. Our study elucidates the nature and range of aortic cell diversity, with implications for the treatment of metabolic pathologies.

Curcumin Induces Endothelium-Dependent Relaxation by Activating Endothelial TRPV4 Channels.

It is well-known that curcumin, as a plant substance, has vascular protective effects. TRPV4 (transient receptor potential vanilloid 4) is a highly Ca2+-selective channel in vascular endothelium. In our study, fluorescent Ca2+ imaging in mesenteric arterial endothelial cells (MAECs) and overexpressed TRPV4 human embryonic kidney (HEK293) cells showed that curcumin dose-dependently stimulated Ca2+ influx. Whole-cell patch clamp proved that curcumin stimulated the TRPV4-mediated currents in TRPV4-HEK293 cells. The TRPV4-specific blocker HC067047 markedly decreased the whole-cell current. Molecular modeling and docking showed that the binding site of curcumin and TRPV4 was mainly in the amino acid sequence LYS340-LEU349 of TRPV4 protein. Furthermore, curcumin dose-dependently induced the endothelium-dependent vessel dilatation in small mesenteric arteries. Therefore, our results demonstrated that curcumin stimulates Ca2+ entry in endothelial cells and improves endothelium-dependent vessel relaxation by activating TRPV4 channels. Moreover, we identified the specific binding sites of curcumin and TRPV4, thereby highlighting its potential therapeutic target of cardiovascular diseases.

Morin induces endothelium-dependent relaxation by activating TRPV4 channels in rat mesenteric arteries.

Morin, a natural flavonol, has been reported to have beneficial pharmacological effects. Although its vascular protective effects have been studied, little is known about its effects on the mesenteric artery and the underlying mechanisms. Transient receptor potential vanilloid type 4 (TRPV4) channels are one of the most important Ca2+-permeable cation channels in vascular endothelial cells and play an important role in regulating rat mesenteric vascular tone. In the present study, the myogenic effects of morin were investigated using wire and pressure myography in the isolated mesenteric artery. Morin induced endothelium-dependent relaxation of isolated rat mesenteric arteries in a concentration-dependent manner. In addition, morin stimulated relaxation by activating TRPV4-mediated Ca2+ influx without affecting the nitric oxide (NO), hydrogen peroxide (H2O2), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) pathways. In primary cultured rat mesenteric artery endothelial cells and over-expressing TRPV4 HEK 293 cells, the TRPV4 inhibitor HC067047 significantly reduced the morin-induced increase in intracellular Ca2+ concentration. Furthermore, in rats with hypertension induced by NꞶ-nitro-L-arginine methyl ester (L-NAME), oral administration of morin (50 mg/kg/day) decreased systolic blood pressure. In L-NAME-induced hypertensive rats, morin significantly improved the relaxation response of the arteries to acetylcholine. Thus, we demonstrated that morin induces endothelium-dependent relaxation in the rat mesenteric artery by acting on TRPV4 channels to mediate Ca2+ influx and attenuate blood pressure in L-NAME-induced hypertension, thereby highlighting the potential of morin in the treatment of hypertension.