Abstract:Aim To explore the effects of exercise during pregnancy on renal structure, function and angiotensin Ⅱ (Ang Ⅱ)/transforming growth factor-β1 (TGF-β1)/connective tissue growth factor (CTGF) signaling pathway in 3-month-old offspring of spontaneously hypertensive rats (SHR), the aim of this study was to provide experimental basis for early intervention of hypertension and protection of key target organs. Methods After mating SHR and WKY rats, pregnant rats were randomly divided into sedentary group (p-WKY-SED, p-SHR-SED) and exercise group (p-WKY-EX, p-SHR-EX). Blood pressure, serum urea nitrogen and creatinine were measured by caudal artery non-invasive blood pressure system and colorimetry in 3-month-old offspring rats. HE staining, Masson staining, ELISA and Western blot were used to detect the renal structure, collagen volume fraction, AngⅡ concentration, renin-angiotension-aldosterone system (RAAS) and protein expression related to fibrogenic signal pathway in 3-month-old rats. Results (1) The systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) of offspring rats in p-SHR-SED group were significantly higher than those in p-WKY-SED group. The SBP, DBP and MAP of SHR male offspring rats were significantly decreased by exercise during pregnancy (P＜0.05), but had no effect on the female offspring rats (P＞0.05). (2) There was no significant difference in serum urea nitrogen and creatinine among the groups (P＞0.05). (3) The glomerular volume and the collagen volume fraction in p-SHR-SED group were significantly higher than those in p-WKY-SED group (P＜0.05), and the glomerular volume and the collagen volume fraction in p-SHR-EX group were significantly lower than those in p-SHR-SED group (P＜0.05). (4) Renal AngⅡ level of offspring rats in p-SHR-SED group was significantly higher than that in p-WKY-SED group, and renal AngⅡ level of offspring rats in p-SHR-EX group was significantly lower than that in p-SHR-SED group (P＜0.05). (5) The expression levels of angiotensinⅡ type 1 receptor (AT1R), TGF-β1 and CTGF protein in p-SHR-SED group were significantly higher than those in p-WKY-SED group (P＜0.05), while the expression levels of angiotensin converting enzyme 2 (ACE2), angiotensinⅡ type 2 receptor (AT2R) and MasR protein in p-SHR-SED group were significantly lower than those in p-WKY-SED group (P＜0.05). Conclusion (1) Exercise during pregnancy can significantly decrease the blood pressure of 3-month-old male offspring rats of hypertensive rats, but has no significant effect on that of 3-month-old female offspring. (2) Exercise during pregnancy may reduce renal fibrosis in 3-month-old female/male offspring of hypertensive rats by regulating RAAS balance and inhibiting AngⅡ /TGF-β1/CTGF signaling pathway.

Abstract:Renal arterial stenosis (RAS) hypertension is one of the common types of secondary hypertension. The main clinical manifestations are increased levels of renin and aldosterone, abnormal renal function and refractory hypertension that is difficult to control by drugs. In this paper, a case with refractory hypertension due to atherosclerotic renal artery stenosis was reported and the relevant literature was reviewed. The patient was a middle-aged male who could not control his blood pressure within the ideal range despite oral administration of amlodipinebesylate, terazosinhydrochloride, irbesartan, carvedilol, metoprololsuccinate, diltiazium hydrochloride and other drugs, requiring continuous pumping of nitroglycerin to lower blood pressure. Furthermore, the examination of renal artery angiography revealed severe stenosis at the origin of the left renal artery. After stent implantation at the renal artery stenosis, blood pressure could be controlled to the standard by oral administration of terazosin hydrochloride, amlodipine besylate and diltiazem hydrochloride only. There are many reasons leading to secondary hypertension. This paper discusses the common causes of renal artery stenosis as a starting point, in order to deepen the understanding of secondary hypertension and reduce the occurrence of missed diagnosis or misdiagnosis.

Abstract:Hypoxia inducible factors (HIF) are hypoxia-sensitive transcription factors that are the primary regulators of the cellular response to hypoxia. Hypoxia inducible factors induce inflammation, lipid metabolism, endothelial dysfunction, proliferation of vascular smooth muscle cells (VSMC), and regulate the development of cardiovascular diseases (CVD). This paper reviews the role of hypoxia inducible factors in CVD and the progress of the mechanism of action in recent years, and discusses the role and mechanism of hypoxia inducible factors on vascular constituent cell types and its relationship with the occurrence and development of CVD. It can provide a reference for analyzing the pathogenesis of CVD and discovering new therapeutic targets. The aim is to provide a theoretical reference for further understanding the role and mechanism of hypoxia inducible factors in the pathogenesis of CVD, and to provide a basis for the design of novel effective therapeutic agents targeting hypoxia inducible factors.

Abstract:Aim To investigate the effect of CDR132L (miR-132 antisense oligonucleotide) on vascular remodeling and function in mice with hypertension and hyperlipidemia, and explore its possible mechanism. Methods A total of 30 8-week-old male C57BL/6 mice were randomly divided into three groups:control group, model group and CDR132L group, with 10 mice in each group. The control group received with a standard diet while the model group and CDR132L group received N-nitro-L-arginine methyl ester (L-NAME) and high-fat diet to induce hypertension and hyperlipidemia. The CDR132L group was administered with intraperitoneal injection of CDR132L at a dose of 20 mg/kg once weekly for six consecutive weeks, whereas the control group and the model group were given intraperitoneal injection of an equivalent volume of normal saline. The tail-cuff method was utilized for blood pressure measurement, blood lipid and glucose levels were assayed by an automatic biochemical analyzer, the thoracic aorta structure was observed by HE staining, endothelium-dependent relaxation of the thoracic aorta was evaluated by the vascular ring test, the expression level of miR-132 in the thoracic aorta was measured by qPCR, the protein expression levels of Gab1 and endothelial nitric oxide synthase (eNOS) in the thoracic aorta were determined by Western blot. Results Compared with the control group, the model group demonstrated notable rises in systolic and diastolic blood pressure, serum triglyceride, total cholesterol levels, and body weight. Moreover, the intima of thoracic aorta and the thickness of vascular wall was uneven, the smooth muscle cells of the tunica media were arranged irregularly, with a large amount of fat deposition in the vascular wall, and the endothelium-dependent relaxation response of thoracic aorta was decreased (P＜0.05). The expression level of miR-132 in the thoracic aorta was significantly increased (P＜0.05), while the expression level of Gab1 and eNOS protein was markedly decreased (P＜0.05). Compared with the model group, the CDR132L group showed no significant differences in systolic and diastolic blood pressure, serum triglyceride and total cholesterol levels, as well as body weight (P＞0.05).However, the CDR132L group exhibited a complete and smooth intima of the thoracic aorta with minimal intravascular lipid deposition, the thickness of the vascular wall was uniform, the smooth muscle cells of the tunica media were arranged orderly, accompanied by enhanced endothelium-dependent relaxation response of the thoracic aorta (P＜0.05). The expression level of miR-132 in the thoracic aorta was significantly decreased (P＜0.05), while the expression levels of Gab1 and eNOS protein were significantly increased (P＜0.05). Conclusion CDR132L can improve vascular remodeling and endothelium-dependent relaxation in hypertensive and hyperlipidemia mice, which may be related to the decrease of miR-132 expression level and the up-regulation of Gab1 and eNOS protein expression levels in the thoracic aorta.

Abstract:Aim To investigate the relationship between triglyceride-glucose (TyG) index and the risk of hypertension in middle-aged and older adults in China, and to provide scientific basis for the prevention and treatment of hypertension. Methods Data were obtained from the China health and retirement longitudinal study (CHARLS) in 2011. A multi-stage stratified sampling method was used to select participants. Restricted cubic spline regression model was used to analyze the dose-response relationship between TyG index and the risk of hypertension. Multivariate unconditional Logistic regression model was used to evaluate the association between TyG index and the risk of hypertension.Results A total of 9 987 subjects were included in the analysis, with an average age of (59.16±9.43) years, including 4 707 males (47.13%). The restricted cubic spline regression model showed that the risk of hypertension increased with the elevation of TyG index, and there was a linear association (overall association test P＜0.000 1, non-linear association test P＝0.201 9). The results of multivariate Logistic regression model showed that compared with Q1 (TyG index＜8.23), the OR(95%CI) of hypertension with Q2 (8.23≤TyG index＜8.59), Q3 (8.59≤TyG index＜9.04) and Q4 (TyG index≥9.04), were 1.09 (0.95～1.26), 1.53 (1.33～1.76) and 1.77 (1.52～2.06), respectively. Conclusions With the increase of TyG index, the risk of hypertension gradually increased. TyG index may be an independent risk factor of hypertension.

Abstract:Aim To investigate the levels of a disintegrin and metalloprotease 10 (ADAM-10) and soluble urokinase plasminogen activator receptor (suPAR) in the serum of hypertension patients with atherosclerosis and their relationship with the severity of disease. Methods From February 2021 to February 3,5 hypertension patients with atherosclerosis who visited our hospital were collected as the study group, and 76 healthy people were collected as control group. The patients in the study group were grouped into mild group (n＝40), moderate group (n＝42) and severe group (n＝43) according to the degree of atherosclerosis, after 60 days of treatment, the patients were grouped into a good prognosis group (n＝74) and a poor prognosis group (n＝51) based on their prognosis. Enzyme linked immunosorbent assay (ELISA) was applied to measure serum ADAM-10 and suPAR levels; Clinical data of patients with different prognosis were compared; Pearson method was applied to analyze the relationship between serum ADAM-10, suPAR levels and carotid intima-media thickness (IMT) in patients with hypertension and atherosclerosis; Multivariate Logistic regression was applied to analyze the influencing factors of poor prognosis in patients with hypertension and atherosclerosis; Receiver operating characteristic (ROC) curve was applied to evaluate the predictive value of ADAM-10 and suPAR alone and jointly for poor prognosis of hypertension with atherosclerosis. Results The levels of serum ADAM-10 and suPAR were significantly higher in the study group than those in control group (P＜0.05); The serum ADAM-10 and suPAR levels in moderate group and severe group were obviously higher than those in mild group (P＜0.05), while the serum ADAM-10 and suPAR levels were obviously higher in severe group than those in moderate group (P＜0.05); The serum ADAM-10 and suPAR levels, left and right IMT, systolic blood pressure, and diastolic blood pressure of patients with poor prognosis were significantly higher than those of patients with good prognosis (P＜0.05); Pearson correlation analysis showed that serum ADAM-10 and suPAR levels in patients with hypertension and atherosclerosis were positively correlated with systolic blood pressure, diastolic blood pressure and IMT (P＜0.001); Logistic regression analysis showed that the increased levels of systolic blood pressure, diastolic blood pressure, ADAM-10, suPAR and IMT were risk factors for poor prognosis of hypertension patients with atherosclerosis (P＜0.05); ROC curve analysis showed that the area under the curve (AUC) of serum ADAM-10 and suPAR levels alone and jointly predicting poor prognosis of hypertension with atherosclerosis was 0.9,0.830 and 0.900, respectively, the combination of the two was superior to their individual predictions (Zcombination-ADAM-10＝2.766, P＝0.006; Zcombination-suPAR＝2.602, P＝0.009).Conclusion The levels of serum ADAM-10 and suPAR in patients with hypertension and atherosclerosis are significantly increased, and are positively correlated with the severity of atherosclerosis. Both of them have a high predictive value for evaluating the prognosis of patients with hypertension and atherosclerosis.

Abstract:Aim To explore the correlation between carotid atherosclerosis (CAS) and neutrophil/lymphocyte ratio (NLR) in patients with early morning hypertension, and to construct a line chart model to predict the risk of CAS in patients with hypertension in the morning. Methods 255 patients with early morning hypertension hospitalized in the Affiliated Hospital of Chengde Medical College from October 2019 to November 2022 were collected, and their basic data, blood routine and blood biochemical indexes were collected. All selected patients need to improve 24-hour ambulatory blood pressure monitoring and carotid artery color ultrasound detection. According to the presence or absence of CAS, all selected patients were divided into morning hypertension with CAS group (n＝197) and morning hypertension without CAS group (n＝58). Multivariate Logistic regression analysis was used to explore the risk factors of early morning hypertension with CAS, and to construct and verify an individual line chart model to predict the risk of early morning hypertension patients with CAS. Results The age, NLR, neutrophils (NE), monocytes (MO), white blood cell (WBC), total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDLC) increased in the early morning hypertension with CAS group compared with those in the morning hypertension group without CAS, while the HDLC decreased(P＜0.05). The results of multivariate Logistic regression analysis showed that the age, NLR and TC were higher in the early morning hypertension with CAS group than those in the early morning hypertension without CAS group, while HDLC was lower; Age, NLR and TC were independent risk factors of early morning hypertension with CAS, while HDLC was independent protective factors of morning hypertension with CAS. Based on the results of multivariate Logistic regression analysis, an individualized line chart model for predicting early morning hypertension with CAS was constructed. The area under the ROC curve of the line chart model was 0.853 (95%CI:0.802～0.904, P＜0.01). The result of Hosmer Lemeshow fit test was χ2=1.665 (P＞0.05). Conclusions There was a positive correlation between NLR and morning hypertension with CAS, and NLR was an independent risk factor for morning hypertension with CAS. The individualized line chart model based on age, NLR, TC and HDLC can effectively predict the risk of hypertension with CAS in the early morning, which provides a theoretical basis for early detection and prevention of atherosclerosis.

Abstract:In September 2024, the “Clinical Practice Guidelines for the Management of Hypertension in China” was officially released by the Chinese Society of Cardiology, Chinese Medical Association and other academic institutions.The guideline encompasses 98 recommendations for 44 key clinical issues in the management of hypertension. This article presents a concise summary of 10 highlights of the guideline, including the scientific foundation of the guideline, the concept and definition of prehypertension, simplified risk stratification for hypertension, antihypertensive treatment initiation timing, antihypertensive targets for different populations, first-line antihypertensive drugs, antihypertensive programs for various clinical complications, non-drug therapies, indications for renal denervation, and screening for secondary hypertension, in order to help doctors better understand the guidelines, promote their implementation, and guide clinical practice.

Abstract:Aim Investigating the effects of exercise during pregnancy on blood pressure and brain ischemia-reperfusion injury in 1-month-old (1M) and 3-month-old (3M) offspring of spontaneously hypertensive rat (SHR). Methods SHR and Wistar Kyoto rats (WKY) were selected, they were paired in a 1∶1 male-to-female ratio within the same strain, and the first day of pregnancy was confirmed by the presence of copulatory plugs and sperm on a vaginal smear. Pregnant rats were randomly divided into pregnancy sedentary group (p-WKY-SED, p-SHR-SED) and pregnancy exercise group (p-WKY-EX, p-SHR-EX). The rats in the exercise group were performed non-weight-bearing swimming for 60 minutes per day, 6 days per week, in water 40 cm deep at a temperature of 34～35 ℃, until the 20th day of pregnancy. The body weight of the pregnant rats, as well as physiological indicators such as fetal weight, body length, and placental efficiency were monitored to reflect the growth and development of the fetus. 1M and 3M offspring were selected as research subjects, non-invasive blood pressure was measured in the tail artery, a rat middle cerebral artery occlusion (MCAO) model was prepared by using the thread embolism method, and the area of cerebral infarction was observed 24 hours after reperfusion. Results (1) Compared with p-WKY-SED group, the body weight of p-SHR-SED pregnant rats was significantly decreased (P＜0.01); there was no significant difference in the litter size among all groups of pregnant rats (P＞0.05). (2) Compared with p-SHR-SED group, exercise during pregnancy can significantly increase the body weight and placental efficiency of both female and male fetal rats in the p-SHR-EX group (P＜0.05), and decrease the weight of the placenta (P＜0.05). (3) Compared with p-WKY-SED group, the body weight of both female and male offspring rats at 1M and 3M was significantly decreased in the p-SHR-SED group, and their blood pressure was significantly increased (P＜0.01); Compared with p-SHR-SED group, exercise during pregnancy had no significant effect on the body weight and blood pressure of 1M offspring in the p-SHR-EX group (P＞0.05), but it could significantly reduce the blood pressure of 3M male offspring in the p-SHR-EX group (P＜0.01); The body weight and blood pressure of 3M male offspring were significantly higher in p-WKY-SED group and p-SHR-SED group than those of female in the same group (P＜0.01). (4) Compared with p-WKY-SED group, the infarct area of MCAO injury in both female and male offspring rats at 1M and 3M was significantly increased in the p-SHR-SED group (P＜0.01); Compared with p-SHR-SED group, exercise during pregnancy can significantly reduce the infarct area of MCAO injury in both female and male offspring at 1M and 3M in the p-SHR-EX group (P＜0.05). Conclusion Aerobic exercise during pregnancy can significantly improve blood pressure in the offspring of hypertensive rats, and reduce their susceptibility to ischemic reperfusion injury in the brain as adults.

Abstract:Aim To investigate the role of myeloid angiotensin type 1 receptor (Mye AT1R) in vascular insulin resistance and vascular injury in deoxycorticosterone acetate (DOCA)/salt-sensitive hypertensive mice. Methods C57BL/6J mice (wild type, WT) and Mye AT1R－/－ mice were randomly divided into WT group, DOCA/salt-sensitive hypertension group (DOCA group), Mye AT1R－/－group and Mye AT1R－/－/DOCA group, 8 in each group. DOCA/salt-sensitive hypertension was induced by left nephrectomy and DOCA sustained-release tablet implantation. Systolic blood pressure (SBP) was measured by tail cuff method. HE staining was used to observe aortic wall thickness, immunofluorescence was used to detect F4/80 (monocyte/macrophage marker) of aorta, RT-PCR and Western blot were used for mRNA and protein expressions of AT1R, proinflammatory factors and insulin signaling molecules. Acetylcholine or insulin-induced endothelium-dependent vasodilation was determined by isolated vascular perfusion system. Results Compared with WT group, in DOCA group, systolic blood pressure increased by 37%, aortic wall thickness increased by 57%, acetylcholine or insulin-induced endothelium-dependent vasodilation decreased by 32% and 36% respectively (P＜0.05), the number of F4/80 positive cells increased by 195%, the protein expression of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α) and phosphorylated c-Jun N-terminal kinase (p-JNK) were significantly increased by 42%, 45% and 32% respectively, the protein expression of p-Akt and p-Enos decreased by 36% in the aorta of DOCA mice (P＜0.05). Specific knockout of myeloid AT1R, aortic thickness decreased by 14%, the number of F4/80 positive cells decreased by 44%, acetylcholine or insulin-induced endothelium-dependent vasodilation improved by 21% and 17% respectively, the protein expression of MCP-1, TNF-α and p-JNK decreased by 52%, 41% and 17% respectively, damaged insulin protein PI3K/Akt/eNOS signaling pathway was reversed, the protein expression of p-Akt and p-eNOS increased by 48% and 42% respectively (P＜0.05) without significant reduction in systolic blood pressure. Conclusion Knockout of Mye AT1R can reduce vascular insulin resistance and vascular injury caused by salt-sensitive hypertension, and its mechanism may be related to inhibition of vascular inflammation caused by macrophage infiltration in vascular wall.