A method for improving high altitude hypertension using a gsmtx4 compound

Abstract

The application discloses a method for improving high altitude hypertension by using a GsMTx4 compound, and the GsMTx4 compound is used as a Piezo1 inhibitor, and the cardiovascular system endothelial cell damage is regulated by BNIP3-mediated mitochondrial autophagy, so that the high altitude hypertension is reduced. The application provides a new treatment target for the damage of the high altitude hypertension endothelial cell, and provides a new technology for the treatment of the high altitude hypertension.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically, it relates to a method for improving high-altitude hypertension using the GsMTx4 compound. Background Technology

[0002] High-altitude hypertension refers to elevated blood pressure (diastolic blood pressure above 90 mmHg and systolic blood pressure above 140 mmHg) that occurs in people who normally live in plains areas after moving to high-altitude areas (above 3000m). In such environments, due to hypoxia and low blood pressure, the incidence of hypertension is higher than in plains areas. A retrospective study involving 16,913 participants reported a significant correlation between altitude and hypertension prevalence; at altitudes above 3000m, the prevalence of hypertension increased by approximately 2% for every 100m increase in altitude. Studies have shown a positive correlation between altitude and blood pressure; for every 1km increase in altitude, blood pressure rises by 17.0 / 9.5 mmHg. More than 100 million people worldwide climb mountains each year, and literature reports that young men first exposed to altitudes of 4500m still have a high incidence of hypertension six months later. These data suggest that high-altitude hypertension has a high prevalence, and long-term high-altitude hypertension can cause damage to target organs such as the heart, brain, kidneys, and blood vessels, seriously threatening human health. Therefore, research into the mechanisms of high-altitude hypertension and its application in treatment is of great significance.

[0003] Endothelial cells play a crucial role in maintaining blood pressure and vascular integrity. Endothelial dysfunction is a significant mechanism in the development and progression of hypertension and its target organ damage. Endothelial cells are distributed throughout the inner walls of blood vessels, forming the first line of defense in the cardiovascular system against internal and external factors. Endothelial cell dysfunction, such as alterations in autophagy and apoptosis, can increase vascular damage. In hypertensive patients, endothelial cell dysfunction, such as impaired secretion of nitric oxide and endothelin, causes vasoconstriction, increases circulatory resistance, and ultimately leads to hypertension. Elevated blood pressure promotes microvascular endothelial cell apoptosis, reduces parallel blood pathways, and enhances peripheral circulatory resistance, ultimately resulting in hypertension. Therefore, endothelial cell damage plays a vital role in the development of hypertension.

[0004] Piezo1 is a mechanosensitive cation channel. Upon mechanical stimulation, Piezo1 facilitates the entry of cations into the cell and converts the mechanosignal into a chemical signal, thereby inducing cellular excitation and signal transduction. As a non-selective cation channel, Piezo1 primarily regulates Ca2+. 2 +(Ca 2+ (interflow), while Ca 2+As a second messenger, downstream signaling pathways play a crucial role in changes such as endothelial cell injury, blood pressure regulation, and vascular tone. GsMTx4, as an inhibitor of Piezo1 channels, binds to the cell membrane, enters the lipid bilayer by inserting its hydrophobic domain, acts directly on the membrane of bone marrow proteins, blocks mechanical forces, and transmits through altered membrane tension, thereby blocking Piezo1 ion channels.

[0005] Piezo1 plays a crucial role in the development and progression of cardiovascular disease. Its vasodilatory effect is based on NO synthesis in endothelial cells, and endothelial Piezo1 can also specifically regulate the contraction of certain blood vessels. Piezo1 is highly expressed in endothelial cells, and its upregulation can induce a series of changes in endothelial cells. Piezo1 can cause pathological changes in endothelial cells by acting upstream of TRPV4, causing changes in shear stress and subsequently leading to pathological changes in endothelial cells. Studies have shown that Piezo1 can also cause mitochondrial damage in vascular endothelial cells.

[0006] However, the regulatory role of Piezo1 in endothelial cells, especially in high-altitude hypertension, remains unclear. Summary of the Invention

[0007] Based on extensive past research, this invention proposes the following hypothesis: Under high-altitude hypertension, Piezo1 cells in endothelial cells are stimulated by pressure, causing their channels to open and resulting in calcium... 2+ Excessive calcium ion influx may cause FOXO3 upregulation, thereby activating BNIP3-mediated mitophagy, while excessive Ca... 2+ Influx promotes mitochondrial dysfunction, ultimately leading to endothelial cell damage. This invention elucidates for the first time the molecular mechanism by which Piezo1 regulates endothelial cell damage through BNIP3-mediated mitophagy, providing a novel therapeutic target for high-altitude hypertension.

[0008] Based on the above findings, the technical solution proposed by this invention to solve the aforementioned technical problems is as follows:

[0009] The first aspect of the present invention provides the use of a Piezo1 inhibitor in the preparation of a drug for treating hypertension.

[0010] Preferably, the Piezo1 inhibitor is a substance that inhibits Piezol activity or reduces Piezol levels;

[0011] More preferably, the substance that inhibits Piezol activity is selected from GsMTx4, carotenoids, or cytochalasin D;

[0012] More preferably, the substance inhibiting Piezol activity is the GsMTx4 polypeptide, the sequence of which is as follows: Gly-Cys-Leu-Glu-Phe-Trp-Trp-Lys-Cys-Asn-Pro-Asn-Asp-Asp-Lys-Cys-Cys-Arg-Pro-Lys-Leu-Lys-Cys-Ser-Lys-Leu-Phe-Lys-Leu-Cys-Asn-Phe-Ser-Phe-NH2.

[0013] A second aspect of the present invention provides the use of a Piezo1 inhibitor in the preparation of a drug for treating high-altitude hypertension.

[0014] Preferably, the Piezo1 inhibitor is a substance that inhibits Piezol activity or reduces Piezol levels;

[0015] More preferably, the substance that inhibits Piezol activity is selected from GsMTx4, carotenoids, or cytochalasin D;

[0016] More preferably, the substance inhibiting Piezol activity is the GsMTx4 polypeptide, the sequence of which is as follows: Gly-Cys-Leu-Glu-Phe-Trp-Trp-Lys-Cys-Asn-Pro-Asn-Asp-Asp-Lys-Cys-Cys-Arg-Pro-Lys-Leu-Lys-Cys-Ser-Lys-Leu-Phe-Lys-Leu-Cys-Asn-Phe-Ser-Phe-NH2.

[0017] A third aspect of the present invention provides the use of a Piezo1 inhibitor in the preparation of a drug for treating vascular endothelial damage caused by high-altitude hypertension.

[0018] Preferably, the Piezo1 inhibitor is a substance that inhibits Piezol activity or reduces Piezol levels.

[0019] More preferably, the substance that inhibits Piezol activity is selected from GsMTx4, carotenoids, or cytochalasin D.

[0020] In a fourth aspect, the present invention provides an application of a BNIP3 inhibitor in the preparation of a drug for treating high-altitude hypertension.

[0021] In a fifth aspect, the present invention provides the use of a BNIP3 inhibitor in the preparation of a drug for treating vascular endothelial damage caused by high-altitude hypertension.

[0022] In this application, "treatment" means to reduce, alleviate or improve the symptoms of a disease or condition, improve underlying metabolic symptoms, inhibit a disease or condition, such as preventing the development of a disease or condition, alleviating a disease or condition, causing the remission of a disease or condition, relieving the condition caused by a disease or condition, or preventing the symptoms of a disease or condition.

[0023] In this application, "GsMTx4" is a spider venom peptide that selectively inhibits cationic-permeable mechanosensitive channels (MSCs) belonging to the Piezo and TRP channel families. GsMTx4 also blocks cationic-selective stretch-activated channels (SACs), attenuating lysophosphatidylcholine (LPC)-induced astrocyte cytotoxicity and microglia reactivity. GsMTx4 is an important pharmacological tool for identifying the roles of excitatory MSCs in normal physiology and pathology. Its sequence is as follows:

[0024] Gly-Cys-Leu-Glu-Phe-Trp-Trp-Lys-Cys-Asn-Pro-Asn-Asp-Asp-Lys-Cys-Cys-Arg-Pro-Lys-Leu-Lys-Cys-Ser-Lys-Leu-Phe-Lys-Leu-Cys-Asn-Phe-Ser-Phe-NH2.

[0025] By adopting the above technical solution, the present invention has the following beneficial effects compared with the prior art.

[0026] This invention uses GsMTx4 as a Piezo1 inhibitor. GsMTx4 regulates endothelial cell damage through BNIP3-mediated mitophagy, thereby reducing high-altitude hypertension. This provides a new therapeutic target for endothelial cell damage in high-altitude hypertension and offers a new technology for the treatment of high-altitude hypertension.

[0027] The specific embodiments of the present invention will now be described in further detail with reference to the accompanying drawings. Attached Figure Description

[0028] The accompanying drawings, which form part of this application, are used to provide a further understanding of the invention. The illustrative embodiments and descriptions of the invention are used to explain the invention, but do not constitute an undue limitation of the invention. Obviously, the drawings described below are merely some embodiments, and those skilled in the art can obtain other drawings based on these drawings without creative effort. In the drawings:

[0029] Figure 1 A bar chart of blood pressure in mice;

[0030] Figure 2 A bar chart showing mouse heart rate;

[0031] Figure 3 A bar chart showing mouse body weight;

[0032] Figure 4 Bar chart showing ET-1 and NO levels in mice;

[0033] Figure 5 The difference between Piezo1 and LC3 in the aortic endothelium of mice;

[0034] Figure 6 The changes in Piezo1 and mitophagy in HAEC (human aortic endothelial cells) under high-altitude conditions are shown in the following figures: [a. Western blot analysis of the expression levels of Piezo1, BNIP3, and LC3Ⅱ / LC3Ⅰ in each group; b. relative expression level of Piezo1; c. relative expression level of BNIP3; d. relative expression level of LC3Ⅱ / LC3Ⅰ].

[0035] Figure 7 The changes in mitophagy in HAEC were analyzed using Western blot to determine the expression levels of BNIP3, LC3Ⅱ / LC3Ⅰ, and Tom20 in each group. The relative expression levels of BNIP3, LC3Ⅱ / LC3Ⅰ, and Tom20 were also analyzed.

[0036] Figure 8 Intracytal Ca in HAEC 2+ Concentration graph;

[0037] Figure 9 Mitochondrial membrane potential in HAEC [a. Confocal fluorescence intensity of mitochondrial membrane potential, b. Flow cytometry of mitochondrial membrane potential];

[0038] Figure 10 Increased mitochondrial ROS levels;

[0039] Figure 11 For the changes in NO and ET-1 in HAEC;

[0040] Figure 12 Changes in HAEC proliferation and migration numbers [a. Transwell migration assay, b. CCK8 assay for cell proliferation activity]

[0041] Figure 13 The effect of Piezo1 on mitophagy;

[0042] Figure 14 The effect of Piezo1 on Ca2+;

[0043] Figure 15 The effects of Piezo1 on mitochondrial function;

[0044] Figure 16 The effect of Piezo1 on endothelial cells.

[0045] Figure 17 To knock down the effect of BNIP3 on mitophagy

[0046] Figure 18 To knock down the effect of BNIP3 on mitochondrial function

[0047] Figure 19 To knock down the effect of BNIP3 on endothelial cell function

[0048] It should be noted that these accompanying drawings and textual descriptions are not intended to limit the scope of the invention in any way, but rather to illustrate the concept of the invention to those skilled in the art by referring to specific embodiments. Detailed Implementation

[0049] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments will be clearly and completely described below with reference to the accompanying drawings. The following embodiments are used to illustrate the present invention, but are not intended to limit the scope of the present invention.

[0050] 1. In vivo experiments

[0051] 1.1 Experimental Procedure

[0052] a. Constructing a high-altitude hypertension mouse model

[0053] Wild-type (WT) C57 mice aged 8-12 weeks were randomly divided into two groups. The normoxic group was housed under normoxic and normobaric conditions; the high-altitude hypertension group was housed in a hypobaric chamber (simulating an altitude of 6000m).

[0054] b. Validation of the high-altitude hypertension model

[0055] Blood pressure (tail clip method), weight, and heart rate of mice were monitored on days 3 and 7, respectively.

[0056] c. Using the Piezo1 inhibitor GsMTx4 (MCE, HY-P1410), we investigated the effect of the Piezo1 inhibitor on blood pressure in mice with high altitude hypertension.

[0057] C57 mice were intraperitoneally injected with GsMTx4 (1 mg / kg, 0.5 mg / kg) and placed in a hypobaric chamber (simulating an altitude of 6000 m). Blood pressure (tail sheath method), weight, and heart rate were monitored on days 3 and 7.

[0058] Detection of d.Piezo1

[0059] Sections of mouse thoracic aortic tissue were prepared, and the differences in Piezo1 in the aortic endothelium were detected by fluorescence staining.

[0060] f. Endothelial cell function testing

[0061] Changes in NO and ET-1 levels were detected in mouse serum.

[0062] 1.2 Experimental Results

[0063] a. Figure 1 The results showed that after feeding mice in a hypobaric chamber (simulating an altitude of 6000m) for 3 and 7 days, their blood pressure increased compared to the control group, with the increase being more significant in mice fed for 7 days (P<0.05). This indicates that the high-altitude hypertension mouse model was successfully established. Under hypobaric conditions, intraperitoneal injection of different doses of GsMTx4 (0.5mg / kg and 1mg / kg) into mice resulted in a decrease in blood pressure, with the decrease being more significant in mice treated with GsMTx4 (1mg / kg) (P<0.05). This demonstrates that GsMTx4 can alleviate the increase in blood pressure caused by high-altitude hypoxia.

[0064] b. Figure 2 The results showed that after feeding mice in a hypobaric chamber (simulating an altitude of 6000m) for 3 and 7 days, the mice's heart rate increased, with a more significant increase on day 7. Intraperitoneal injection of GsMTx4 (1mg / kg) into the mice resulted in a more significant decrease in blood heart rate (P<0.05), indicating that GsMTx4 can alleviate the increased heart rate caused by high-altitude hypoxia.

[0065] c. Figure 3 The results showed that mice fed in a hypobaric chamber (simulating an altitude of 6000m) for 3 and 7 days experienced a decrease in body weight, with a more significant decrease observed after 7 days. Intraperitoneal injection of GsMTx4 (1 mg / kg) into the mice did not result in a significant change in body weight.

[0066] d. Changes in mouse endothelial function

[0067] Figure 4 Mice were fed in a hypobaric chamber (simulating an altitude of 6000m) for 7 days. Blood samples were taken from the eyeballs to measure nitric oxide (NO) and endothelin-1 (ET-1). Increased NO and ET-1 levels indicated impaired endothelial function. The elevated NO levels may be a compensatory increase in NO levels to adapt to hypoxia after high-altitude hypoxia, thus dilating blood vessels. Intraperitoneal injection of GsMTx4 into mice reduced serum NO and ET-1 levels. This suggests that GsMTx4 can alleviate endothelial cell damage caused by high-altitude hypoxia.

[0068] f. See Figure 5The study involved preparing sections of mouse aortic tissue and detecting differences in Piezo1 and LC3 levels in the aortic endothelium using fluorescent staining. Hypoxia increased the expression of Piezo1 and LC3 in aortic endothelial cells, while the addition of GsMTx4 (1 mg / kg) decreased their expression. This indicates that high-altitude environments lead to increased Piezo1 expression and enhanced mitophagy, and GsMTx4 can alleviate this damage.

[0069] 2. In vitro experiments: The preliminary study of this invention explored the role of Piezo1 in endothelial cells of high-altitude hypertension: Under high-altitude hypertension conditions, endothelial cell damage may be related to Piezo1 activation of BNIP3-mediated mitophagy. Specific results are as follows:

[0070] 2-1 A high-altitude hypertension cell model was established by stimulating human aortic endothelial cells (HAECs) with hypoxia and pressure. Compared with the control group, Piezo1 expression in HAECs was significantly enhanced under hypoxia and pressure conditions. Cells were stimulated under hypoxia and pressure for different time periods (0h, 12h, 24h, 36h, 48h), and mitophagy was most pronounced after 24 hours of stimulation. In the high-altitude hypertension model, Piezo1 overexpression induced calcium ion influx, increasing intracytoplasmic calcium ion concentration. Mitochondrial function was altered: enhanced mitophagy, decreased mitochondrial membrane potential, and increased mitochondrial reactive oxygen species. Endothelial cell function was altered: decreased cell proliferation, increased NO, and increased ET-1 levels.

[0071] (1) Piezo1 expression in HAEC cells after hypoxia + pressure simulated high-altitude conditions

[0072] like Figure 6 As shown, HAEC was divided into the following four groups: control group, hypoxia group, pressure group, and hypoxia + pressure group. Western blot showed that after simulating high-altitude hypertension conditions, the hypoxia + pressure group showed the most significant increase in Piezo1 in human aortic endothelial cells compared with the control group, and correspondingly, the changes in mitophagy were also the most significant (the increases in BNIP3 and LC3 were the most significant).

[0073] (2) Changes in mitophagy in HAEC

[0074] like Figure 7 As shown, Western blot analysis revealed that after hypoxia-induced high-altitude hypertension, compared with the control group, mitophagy exhibited different trends with varying stimulation time. The results showed that mitophagy was strongest at 24 hours.

[0075] (3) Intracellular Ca in HAEC 2+ concentration

[0076] like Figure 8 As shown in the flow cytometry results, compared with the control group, the cytoplasmic calcium in HAEC cells was significantly higher in the hypoxia-stress group. 2+ Concentration increases.

[0077] (4) Mitochondrial membrane potential in HAEC

[0078] like Figure 9 As shown in Figure a: Confocal results show that the mitochondrial membrane potential (JC-1) is decreased in the hypoxia pressure group compared with the control group. Figure b: Flow cytometry results show that the mitochondrial membrane potential (JC-1) is decreased in the hypoxia pressure group compared with the control group.

[0079] (5) Increased mitochondrial ROS content in HAEC

[0080] like Figure 10 As shown in the flow cytometry results, the concentration of ROS in the cytoplasm of HAEC cells increased in the hypoxia pressure group compared with the control group.

[0081] (6) Changes in ET-1 in HAEC

[0082] like Figure 11 As shown in the figure, compared with the control group, Figure a shows that the NO concentration in the hypoxia pressure group is reduced, and Figure b shows that the ET-1 concentration in the hypoxia pressure group is increased.

[0083] (7) Changes in HAEC proliferation and migration numbers

[0084] like Figure 12 As shown in the Transwell migration assay, the number of migrating HAECs in the normoxic and hypoxic groups were 217.3±11.73 and 392.7±19.8, respectively. Compared with the control group, the number of migrating cells in the hypoxic HAECs increased (Figure a). The CCK8 assay showed that cell proliferation activity increased (Figure b).

[0085] 2-2 Changes in human aortic endothelial cells were observed after stimulation with a Piezo1 agonist (Yoda1) and an inhibitor (GsMTx4). Under hypoxic-stress conditions, the addition of the Piezo1 agonist (Yoda1) showed enhanced mitophagy by Western blotting and an increase in autophagosomes and lysosomes by immunofluorescence. The addition of the Piezo1 inhibitor (GsMTx4) showed decreased mitophagy by Western blotting and a decrease in autophagosomes and lysosomes by immunofluorescence. This indicates that GsMTx4 can alleviate the increased mitophagy caused by altitude stress.

[0086] Under hypoxia and stress conditions, changes in mitochondrial function were observed: The addition of a Piezo1 agonist (Yoda1) increased ROS, decreased mitochondrial membrane potential, and decreased ATP. The addition of a Piezo1 inhibitor (GsMTx4) decreased ROS, increased mitochondrial membrane potential, and increased ATP, indicating that the Piezo1 inhibitor can alleviate the mitochondrial functional changes caused by high-altitude stress.

[0087] Under hypoxic and stress conditions, changes in endothelial cell function were observed: After adding a Piezo1 agonist (Yoda1), ET-1 increased, NO decreased, and Transewell analysis showed enhanced cell migration. After adding a Piezo1 inhibitor (GsMTx4), ET-1 decreased, NO increased, and Transewell analysis showed weakened cell migration. This indicates that Piezo1 inhibitors can alleviate endothelial cell dysfunction caused by high-altitude stress.

[0088] (8) Effects of Piezo1 on mitophagy

[0089] like Figure 13 As shown in Figure a, Westen blot results indicate that under hypoxic stress, the addition of a Piezo1 agonist (Yoda1) increases BNIP3, FOXO3a, and LC3II / LC3I ratio, while decreasing Tom20. The addition of a Piezo1 inhibitor (GsMTx4) decreases FOXO3a, BNIP3, and LC3II / LC3I ratio, while increasing Tom20. Figure b indicates that under hypoxic stress, the addition of a Piezo1 agonist (Yoda1) increases mitochondrial lysosomes, while the addition of a Piezo1 inhibitor (GsMTx4) decreases mitochondrial lysosomes.

[0090] (9) Piezo1 on Ca 2+ Impact

[0091] like Figure 14 As shown, flow cytometry results indicate that after the addition of the Piezo1 agonist (Yoda1), the cytoplasmic calcium in HAEC cells decreased. 2+ Increased concentration. After the addition of the Piezo1 inhibitor (GsMTx4), HAEC cytoplasmic Ca2+ concentration increased. 2+ The concentration decreased.

[0092] (10) Effects of Piezo1 on mitochondrial function

[0093] like Figure 15As shown in the flow cytometry results, ROS increased after the addition of the Piezo1 agonist (Yoda1) compared to the control group. ROS decreased after the addition of the Piezo1 inhibitor (GsMTx4) (Figure a). Mitochondrial membrane potential decreased after the addition of the Piezo1 agonist (Yoda1), and increased after the addition of the Piezo1 inhibitor (GsMTx4) (Figure b). ATP decreased after the addition of the Piezo1 agonist (Yoda1), and increased after the addition of the Piezo1 inhibitor (GsMTx4) (Figure c).

[0094] (11) Effects of Piezo1 on endothelial cells

[0095] like Figure 16 As shown in Figure a, compared with the control group, the addition of the Piezo1 agonist (Yoda1) resulted in a decrease in NO levels, while the addition of the Piezo1 inhibitor (GsMTx4) resulted in an increase in NO levels (Figure a). Transwell assays showed that the addition of the Piezo1 agonist (Yoda1) increased cell migration, while the addition of the Piezo1 inhibitor (GsMTx4) decreased cell migration (Figure b). Compared with the control group, the addition of the Piezo1 agonist (Yoda1) resulted in an increase in ET-1 levels, while the addition of the Piezo1 inhibitor (GsMTx4) resulted in a decrease in ET-1 levels (Figure c).

[0096] 2-3 Hypoxia + Pressure (hereinafter referred to as the hypoxia group) conditions, after knocking down BNIP3, the changes in human aortic endothelial cells were observed.

[0097] (12) Changes in mitophagy after BNIP3 knockdown, such as Figure 17 As shown, qPCR showed that HAEC knocked down BNIP3 (Fig. a), and Western blot showed that, compared with the hypoxia group, knocking down BNIP3 under hypoxic conditions reduced mitophagy (Fig. b).

[0098] (13) Changes in mitochondrial function after BNIP3 knockdown, such as Figure 18 As shown, knocking down BNIP3 under hypoxic conditions resulted in increased mitochondrial membrane potential (Fig. a), decreased ROS (Fig. b), and increased ATP (Fig. c) compared to the hypoxic group. This indicates that knocking down BNIP3 can alleviate hypoxia-induced mitochondrial functional damage.

[0099] (14) Changes in cell function after BNIP3 knockdown, such as Figure 19As shown, knocking down BNIP3 under hypoxic conditions resulted in increased NO levels in endothelial cells (Fig. a), decreased ET-1 levels (Fig. b), and reduced cell migration ability as observed by Transewell assays (Fig. c) compared to the hypoxia group. This indicates that knocking down BNIP3 can alleviate hypoxia-induced endothelial cell dysfunction.

[0100] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-described technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes, and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. The application of Piezo1 inhibitors in the preparation of drugs for treating high-altitude hypertension, characterized in that, The substance that inhibits Piezol activity is the GsMTx4 polypeptide, whose sequence is shown below: Gly-Cys-Leu-Glu-Phe-Trp-Trp-Lys-Cys-Asn-Pro-Asn-Asp-Asp-Lys-Cys-Cys-Arg-Pro-Lys-Leu-Lys-Cys-Ser-Lys-Leu-Phe-Lys-Leu-Cys-Asn-Phe-Ser-Phe-NH2.

2. The application according to claim 1, characterized in that, The dosage of the Piezo1 inhibitor is 0.5-1.5 mg / kg.

3. The application of Piezo1 inhibitors in the preparation of drugs for treating vascular endothelial damage caused by high-altitude hypertension, characterized in that, The substance that inhibits Piezol activity is the GsMTx4 polypeptide, whose sequence is shown below: Gly-Cys-Leu-Glu-Phe-Trp-Trp-Lys-Cys-Asn-Pro-Asn-Asp-Asp-Lys-Cys-Cys-Arg-Pro-Lys-Leu-Lys-Cys-Ser-Lys-Leu-Phe-Lys-Leu-Cys-Asn-Phe-Ser-Phe-NH2; The dosage of the Piezo1 inhibitor is 0.5-1.5 mg / kg.

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