Humans ; Blood Pressure/physiology* ; Renal Insufficiency, Chronic ; Hypertension/drug therapy* ; Antihypertensive Agents/therapeutic use*

Chaihu Jia Longgu Muli Decoction was firstly recorded in Treatise on Cold Damage(ZHANG Zhong-jing, Eastern Han dynasty). According to this medical classic, it is originally used in the treatment of the Shaoyang and Yangming syndrome. Based on the modern pathophysiological mechanism, this study interpreted the classic provisions of Chaihu Jia Longgu Muli Decoction. Original records of "chest fullness" "annoyance" "shock" "difficult urination" "delirium" "heavy body and failing to turn over" all have profound pathophysiological basis, involving disorders in cardiovascular, respiratory, nervous, and mental systems. This formula is widely used, which can be applied to treat epilepsy, cerebral arteriosclerosis, cerebral infarction, and other cerebrovascular diseases, hypertension, arrhythmia, and other cardiovascular diseases, insomnia, constipation, anxiety, depression, cardiac neurosis and other acute and chronic diseases as well as diseases in psychosomatic medicine. The clinical indications include Bupleuri Radix-targeted syndrome such as fullness and discomfort in chest and hypochondrium, bitter taste mouth, dry throat, and dizziness, the insomnia, anxiety, depression, susceptibility to fright, upset, dreamfulness and other psychiatric symptoms, red tongue, thick and yellow tongue coating, and wiry hard and powerful pulse. This formula was found to be used in combination with other formulas, such as Gualou Xiebai Decoction, Wendan Decoction, Zhizhu Pills, Juzhijiang Decoction, Suanzaoren Decoction, and Banxia Baizhu Tianma Decoction.
Humans ; Sleep Initiation and Maintenance Disorders/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/drug therapy* ; Syndrome ; Arrhythmias, Cardiac/drug therapy* ; Medicine, Chinese Traditional

Hypertension and its target organ damage have become a major public health problem. Sexual dysfunction is a new problem in the treatment of modern hypertension. Modern pathophysiological studies have shown that hypertension can lead to sexual dysfunction. In addition, three major hypotensive drugs represented by diuretics can also lead to sexual dysfunction. In traditional Chinese medicine(TCM), hypertension belongs to "vertigo" "headache" "head wind", etc. In the past, the understanding of the TCM pathogenesis of hypertension was mainly from the perspectives of "liver wind" and "Yang hyperactivity". However, based on the in-depth research on ancient and modern literature and medical records and many years of clinical practice, it has been identified that kidney deficiency was the key pathogenesis. Hypertension complicated with sexual dysfunction belongs to the category of kidney deficiency syndrome in TCM, especially the deficiency of kidney Yin. Previous studies by other research groups showed that Yin-enriching and kidney-tonifying method could effectively reduce blood pressure, improve sexual dysfunction, reverse risk factors, and protect target organs. This article systematically discussed the TCM understanding, modern pathophysiological mechanism, and the clinical treatment strategy of kidney-tonifying drugs(single drugs and compounds) in the treatment of hypertension complicated with sexual dysfunction in order to provide a scientific basis for kidney-tonifying method in the treatment of hypertension complicated with sexual dysfunction.
Humans ; Antihypertensive Agents/therapeutic use* ; Medicine, Chinese Traditional ; Hypertension/drug therapy* ; Blood Pressure ; Risk Factors ; Drugs, Chinese Herbal/therapeutic use*

This study aims to investigate the effect and mechanism of arctigenin(ARC) in the treatment of vascular endothelial injury in rats with pregnancy-induced hypertension(PIH). Fifty SD rats pregnant for 12 days were randomly assigned into a control group, a model group, an ARC group, a rapamycin(RAP, autophagy inducer) group, and an ARC+3-methyladenine(3-MA, autophagy inhibitor) group, with 10 rats in each group. The rats in the other groups except the control group were intraperitoneally injected with nitrosyl-L-arginine methyl ester(50 mg·kg~(-1)·d~(-1)) to establish the PIH model on the 13th day of pregnancy. On the 15th day of pregnancy, the rats in ARC, RAP, and ARC+3-MA groups were intraperitoneally injected with ARC(50 mg·kg~(-1)·d~(-1)), RAP(1 mg·kg~(-1)·d~(-1)), and 3-MA(15 mg·kg~(-1)·d~(-1))+ARC(50 mg·kg~(-1)·d~(-1)), respectively. The pregnant rats in the control group and the model group were intraperitoneally injected with the same amount of normal saline. The blood pressure and 24 h urine protein(24 h-UP) of pregnant rats in each group were measured before and after intervention. Cesarean section was performed to terminate pregnancy on day 21, and the body weight and body length of fetal rats were compared among groups. Hematoxylin-eosin(HE) staining was employed to observe the pathological changes of placenta. The expression of endothelin-1(ET-1) and endothelial nitric oxide synthase(eNOS) in placenta was detected by immunohistochemistry. The serum levels of ET-1 and nitric oxide(NO) were determined with corresponding kits. The expression of microtubule-associated protein 1 light chain 3(LC3), Beclin-1, NOD-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein with CARD domain(ASC), caspase-1, interleukin(IL)-1β, and IL-18 was determined by immunofluorescence and Western blot. The level of reactive oxygen species(ROS) in placenta was measured by fluorescence staining. The results showed that on day 12 of pregnancy, the blood pressure and 24 h-UP had no significant differences among groups. On days 15, 19, and 21, the blood pressure and 24 h-UP in the model group were higher than those in the control group(P<0.05). On days 19 and 21, the blood pressure and 24 h-UP in ARC group and RAP group were lower than those in the model group(P<0.05), and they were higher in the ARC+3-MA group than in the ARC group(P<0.05). On day 21, the model group had lower body weight and body length of fetal rats(P<0.05), higher serum level of ET-1, and lower serum level of NO(P<0.05) than the control group. Moreover, the placental tissue showed typical pathological damage, down-regulated expression of LC3-Ⅱ/LC3-Ⅰ, Beclin-1 and eNOS(P<0.05), up-regulated expression of ET-1, NLRP3, ASC, caspase-1, IL-1β, and IL-18(P<0.05), and elevated ROS level. Compared with the model group, ARC and RAP groups showed increased body weight and body length of fetal rats(P<0.05), lowered serum level of ET-1, elevated serum level of NO(P<0.05), reduced pathological damage of placental tissue, up-regulated expression of LC3-Ⅱ/LC3-Ⅰ, Beclin-1, and eNOS(P<0.05), down-regulated expression of ET-1, NLRP3, ASC, caspase-1, IL-1β, and IL-18(P<0.05), and lowered ROS level. Compared with ARC group, 3-MA reversed the effects of ARC on the above indicators. In conclusion, ARC can inhibit the activation of NLRP3 inflammasome and mitigate vascular endothelial damage in PIH rats by inducing autophagy of vascular endothelial cells.
Female ; Pregnancy ; Animals ; Rats ; Humans ; Rats, Sprague-Dawley ; Hypertension, Pregnancy-Induced/drug therapy* ; Endothelial Cells ; Inflammasomes ; Interleukin-18 ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Beclin-1 ; Cesarean Section ; Reactive Oxygen Species ; Placenta ; Caspase 1 ; Autophagy

Primary aldosteronism (PA) is the most common form of secondary hypertension, with its main manifestations including hypertension and hypokalemia. Early identification of PA is extremely important as PA patients can easily develop cardiovascular complications such as atrial fibrillation, stroke, and myocardial infarction. The past decade has witnessed the rapid advances in the genetics of PA, which has shed new light on PA treatment. While surgery is the first choice for unilateral diseases, bilateral lesions can be treated with mineralocorticoid receptor antagonists (MRAs). The next-generation non-steroidal MRAs are under investigations. New medications including calcium channel blockers, macrophage antibiotics, and aldosterone synthase inhibitors have provided a new perspective for the medical treatment of PA.
Humans ; Hyperaldosteronism/complications* ; Adrenalectomy/adverse effects* ; Aldosterone/therapeutic use* ; Hypertension/drug therapy* ; Mineralocorticoid Receptor Antagonists/therapeutic use*

OBJECTIVE: To describe the disease characteristics of osteonecrosis of the femoral head (ONFH) in patients with systemic lupus erythematosus (SLE) who experiencing prolonged glucocorticoid (GC) exposure. METHODS: Between January 2016 and June 2019, 449 SLE patients meeting the criteria were recruited from multiple centers. Hip MRI examinations were performed during screening and regular follow-up to determine the occurrence of ONFH. The cohort was divided into ONFH and non-ONFH groups, and the differences in demographic baseline characteristics, general clinical characteristics, GC medication information, combined medication, and hip clinical features were compared and comprehensively described. RESULTS: The age at SLE diagnosis was 29.8 (23.2, 40.9) years, with 93.1% (418 cases) being female. The duration of GC exposure was 5.3 (2.0, 10.5) years, and the cumulative incidence of SLE-ONFH was 9.1%. Significant differences ( P<0.05) between ONFH and non-ONFH groups were observed in the following clinical characteristics: ① Demographic baseline characteristics: ONFH group had a higher proportion of patients with body mass index (BMI)<20 kg/m ² compared to non-ONFH group. ② General clinical characteristics: ONFH group showed a higher proportion of patients with cutaneous and renal manifestations, positive antiphospholipid antibodies (aPLs) and anticardiolipin antibodies, severe SLE patients [baseline SLE Disease Activity Index 2000 (SLEDAI-2K) score ≥15], and secondary hypertension. Fasting blood glucose in ONFH group was also higher. ③ GC medication information: ONFH group had higher initial intravenous GC exposure rates, duration, cumulative doses, higher cumulative GC doses in the first month and the first 3 months, higher average daily doses in the first 3 months, and higher proportions of average daily doses ≥15.0 mg/d and ≥30.0 mg/d, as well as higher full-course average daily doses and proportion of full-course daily doses ≥30.0 mg/d compared to non-ONFH group. ④ Combined medications: ONFH group had a significantly higher rate of antiplatelet drug use than non-ONFH group. ⑤ Hip clinical features: ONFH group had a higher proportion of hip discomfort or pain and a higher incidence of hip joint effusion before MRI screening than non-ONFH group. CONCLUSION The incidence of ONFH after GC exposure in China's SLE population remains high (9.1%), with short-term (first 3 months), medium-to-high dose (average daily dose ≥15 mg/d) GC being closely associated with ONFH. Severe SLE, low BMI, certain clinical phenotypes, positive aPLs, and secondary hypertension may also be related to ONFH.
Female ; Male ; Humans ; Glucocorticoids/adverse effects* ; Incidence ; Femur Head ; Prospective Studies ; Femur Head Necrosis/epidemiology* ; Lupus Erythematosus, Systemic/chemically induced* ; Hypertension/drug therapy*

Primary myelofibrosis (PMF) is easily confused with cirrhosis, due to its main clinical manifestations of splenomegaly and the blood cytopenia. This review focuses on clinical studies to identify primary myelofibrosis and cirrhosis related portal hypertension, to analyze the differences between the two diseases, in order to distinguish PMF and cirrhosis from the pathogenesis, clinical manifestations, laboratory examinations and treatment principles, and simultaneously improve clinicians' understanding of PMF, which is a reference for exploring the early screening or diagnostic indicators of PMF, also provides a clinical basis for the application of new targeted drugs such as ruxolitinib.
Humans ; Primary Myelofibrosis/drug therapy* ; Hypertension, Portal/complications* ; Liver Cirrhosis/pathology* ; Splenomegaly/pathology* ; Anemia

OBJECTIVE: To explore the protective effect and mechanism of Kuntai (KT) Capsule on angiotensin II (Ang II)-induced hypertension in ovariectomized (OVX) rats. METHODS: Fifty-four rats were randomly divided into 6 groups according to a random number table, 9 in each group: control, OVX sham+Ang II, OVX, OVX+Ang II, OVX+Ang II +E₂, and OVX+Ang II +KT. OVX rats model was constructed by retroperitoneal bilateral ovariectomy. After 4 weeks of pretreatment with KT Capsule [0.8 g/(kg·d) and 17- β -estradiol (E₂, 1.2 mg/(kg·d)] respectively, Ang II was injected into a micro-osmotic pump with a syringe to establish a hypertensive rat model. Blood pressure of rat tail artery was measured in a wake state of rats using a non-invasive sphygmomanometer. Blood pressure changes were compared between the intervention groups (OVX+Ang II +KT, OVX+Ang II +E₂) and the negative control group (OVX+Ang II). Serum malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were detected respectively. The expressions of oxidative stress-related protein superoxide dismutase2 (SOD2) and anti-thioredoxin (TRX), autophagy marker protein [beclin1, light chain (LC) 3 II/I ratio and autophagy canonical pathway protein phosphatidylinositol 3-kinase (PI3K)/serine/threonine kinase (AKT)-mammalian target of rapamycin (mTOR)] were evaluated by Western blotting. RESULTS: Compared with the OVX+Ang II group, the systolic blood pressure of OVX+Ang II +KT group was significantly lowered (P<0.05) but not the diastolic blood pressure. Besides, SOD2 and TRX protein levels in mycardial tissues were significantly reduced in the OVX+Ang II +KT group compared with the OVX+Ang II group (P<0.05). Oxidative stress serum markers MDA and SOD were down- and up-regulated in the OVX+Ang II +KT group, respectively (P<0.05). Compared with OVX+Ang II group, the levels of cardiac proteins beclin-1 and LC3II/LC3 I in OVX+Ang II +KT group were also up-regulated (P<0.05), and the expression levels of p-PI3K, p-AKT and mTOR protein were down-regulated (P<0.05). CONCLUSION KT could protect blood pressure of Ang II-induced OVX rats by inhibiting oxidative stress and up-regulating protective autophagy.
Female ; Rats ; Animals ; Humans ; Angiotensin II ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Hypertension/drug therapy* ; Estradiol/pharmacology* ; Superoxide Dismutase ; Ovariectomy ; Mammals/metabolism*

Humans ; Hypertension, Pulmonary/drug therapy* ; Antihypertensive Agents/therapeutic use* ; Cardiology ; Hypertension/drug therapy*

In this study, we investigated the effects of Panax notoginseng saponins (PNS) on pulmonary vascular remodeling and ADAM10/Notch3 pathway in pulmonary arterial hypertension (PAH). PAH rat model was established, and male Sprague Dawley (SD) rats were randomly divided into control group, monocrotaline (MCT) group and MCT+PNS group, with 10 rats in each group. Rats in the control group were intraperitoneally injected with equal volume of normal saline. Rats in the MCT group was injected intraperitoneally with 60 mg/kg MCT on the first day, and then with the same volume of normal saline every day. Rats in the MCT+PNS group was injected intraperitoneally with 60 mg/kg MCT on the first day, and then with 50 mg/kg PNS every day. The modeling time of each group lasted for 21 days. After the model was established, the mean pulmonary artery pressure (mPAP) was measured by right heart catheterization technique, the right ventricular hypertrophy index (RVHI) was calculated, the microscopic morphology and changes of pulmonary vascular wall were observed by HE and Masson staining, and the expressions of ADAM10, Notch3, Hes-1, P27, PCNA, Caspase-3 proteins and mRNA in pulmonary vascular tissue of rats were detected by Western blot and qPCR. The expression and localization of Notch3 and α-SMA were detected by immunofluorescence staining. The protein expression of ADAM10 was detected by immunohistochemical staining. The results showed that compared with the control group, mPAP, RVHI, pulmonary vessels and collagen fibers in the MCT group were significantly increased, the expressions of ADAM10, Notch3, Hes-1, and PCNA protein and mRNA were significantly increased, while the expressions of P27 and Caspase-3 protein and mRNA were decreased significantly. Compared with the MCT group, mPAP and RVHI were significantly decreased, pulmonary vessels were significantly improved and collagen fibers were significantly reduced, the expressions of protein and mRNA of ADAM10, Notch3, Hes-1, and PCNA were decreased in MCT+PNS group, but the expressions of protein and mRNA of P27 and Caspase-3 were increased slightly. The results of immunofluorescence showed that Notch3 and α-SMA staining could overlap, which proved that Notch3 was expressed in smooth muscle cells. The expression of Notch3 in the MCT group was increased significantly compared with that in the control group, while PNS intervention decreased the expression of Notch3. Immunohistochemical staining showed that compared with the control group, the amount of ADAM10 in the MCT group was increased significantly, and the expression of ADAM10 in the MCT+PNS group was decreased compared with the MCT group. These results indicate that PNS can improve the PAH induced by MCT in rats by inhibiting ADAM10/Notch3 signaling pathway.
Animals ; Male ; Rats ; Caspase 3/metabolism* ; Collagen ; Disease Models, Animal ; Hypertension, Pulmonary/drug therapy* ; Monocrotaline/adverse effects* ; Panax notoginseng/chemistry* ; Proliferating Cell Nuclear Antigen/pharmacology* ; Pulmonary Arterial Hypertension ; Pulmonary Artery/metabolism* ; Rats, Sprague-Dawley ; Receptor, Notch3/genetics* ; RNA, Messenger ; Saline Solution ; Signal Transduction ; Saponins/pharmacology*