Objective Angiotensin Ⅱ (Ang Ⅱ)-induced vascular damage is a major risk of hypertension. However, the underlying molecular mechanism of AngⅡ-induced vascular damage is still unclear. In this study, we explored the novel mechanism associated with Ang II-induced hypertension. Methods We treated 8- to 12-week-old C57BL/6J male mice with saline and Ang Ⅱ(0.72 mg/kg·d) for 28 days, respectively. Then the RNA of the media from the collected mice aortas was extracted for transcriptome sequencing. Principal component analysis was applied to show a clear separation of different samples and the distribution of differentially expressed genes was manifested by Volcano plot. Functional annotations including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed to reveal the molecular mechanism of Ang Ⅱ-induced hypertension. Finally, the differentially expressed genes were validated by using quantitative real-time PCR. Results The result revealed that a total of 773 genes, including 599 up-regulated genes and 174 down-regulated genes, were differentially expressed in the aorta of Ang Ⅱ-induced hypertension mice model. Functional analysis of differentially expressed genes manifested that various cellular processes may be involved in the Ang Ⅱ-induced hypertension, including some pathways associated with hypertension such as extracellular matrix, inflammation and immune response. Interestingly, we also found that the differentially expressed genes were enriched in vascular aging pathway, and further validated that the expression levels of insulin-like growth factor 1 and adiponectin were significantly increased (P<0.05). Conclusion We identify that vascular aging is involved in Ang Ⅱ-induced hypertension, and insulin-like growth factor 1 and adiponectin may be important candidate genes leading to vascular aging.
Aging ; Angiotensin II ; Animals ; Aorta/physiopathology* ; Blood Pressure/genetics* ; Gene Expression Profiling/methods* ; Gene Ontology ; Hypertension/genetics* ; Male ; Mice, Inbred C57BL ; Reverse Transcriptase Polymerase Chain Reaction

Lymphangioleiomyomatosis (LAM) is a rare diffuse cystic lung disease. Knowledge on LAM-related pulmonary hypertension (PH) is limited. This study aimed to analyze the clinical characteristics of LAM with elevated pulmonary artery pressure (PAP) and evaluate the potential efficacy of sirolimus. The study involved 50 LAM patients who underwent echocardiography. According to the tricuspid regurgitation velocity (TRV), these patients were divided into the TRV ⩽ 2.8 m/s group and TRV > 2.8 m/s group. Both groups comprised 25 females with an average age of 38.6 ± 8.1 and 41.5 ± 8.9 years. In the TRV > 2.8 m/s group, the estimated systolic PAP (SPAP) was significantly elevated (52.08 ± 12.45 mmHg vs. 30.24 ± 5.25 mmHg, P < 0.01). Linear analysis showed that SPAP was correlated with forced expiratory volume in 1 s (FEV), diffusing capacity of the lungs for carbon monoxide, alveolar arterial oxygen gradient (PO), and 6 min walking distance (r =-0.392, -0.351, 0.450, and -0.591, respectively; P < 0.05), in which PO was a risk factor for SPAP elevation (β = 0.064, OR = 1.066, P < 0.05). Moreover, in 10 patients who received sirolimus therapy, SPAP decreased from 57.0 12.6 mmHg to 35.2 ± 11.1 mmHg. The study showed that LAM patients with PH exhibit poor pulmonary function and hypoxemia and may benefit from sirolimus treatment.
Adult ; Carbon Monoxide ; analysis ; Echocardiography ; Exercise Test ; Female ; Hemodynamics ; Humans ; Hypertension, Pulmonary ; physiopathology ; therapy ; Logistic Models ; Lymphangioleiomyomatosis ; physiopathology ; therapy ; Male ; Middle Aged ; Multivariate Analysis ; Oxygen ; blood ; therapeutic use ; Respiratory Function Tests ; Sirolimus ; therapeutic use

The hypothalamic paraventricular nucleus (PVN) is a crucial region involved in maintaining homeostasis through the regulation of cardiovascular, neuroendocrine, and other functions. The PVN provides a dominant source of excitatory drive to the sympathetic outflow through innervation of the brainstem and spinal cord in hypertension. We discuss current findings on the role of the PVN in the regulation of sympathetic output in both normotensive and hypertensive conditions. The PVN seems to play a major role in generating the elevated sympathetic vasomotor activity that is characteristic of multiple forms of hypertension, including primary hypertension in humans. Recent studies in the spontaneously hypertensive rat model have revealed an imbalance of inhibitory and excitatory synaptic inputs to PVN pre-sympathetic neurons as indicated by impaired inhibitory and enhanced excitatory synaptic inputs in hypertension. This imbalance of inhibitory and excitatory synaptic inputs in the PVN forms the basis for elevated sympathetic outflow in hypertension. In this review, we discuss the disruption of balance between glutamatergic and GABAergic inputs and the associated cellular and molecular alterations as mechanisms underlying the hyperactivity of PVN pre-sympathetic neurons in hypertension.
Animals ; Blood Pressure ; physiology ; Excitatory Postsynaptic Potentials ; physiology ; Humans ; Hypertension ; physiopathology ; Hypothalamus ; physiology ; Neurons ; physiology ; Paraventricular Hypothalamic Nucleus ; physiology

OBJECTIVE: To evaluate the efficacy and safety of blood-letting therapy (BLT) in treatment of hypertension. METHODS: A comprehensive electronic and manual bibliographic searches were performed in Cochrane Central Register of Controlled Trials, Excerpt Medica Database (EMBASE), PubMed, China National Knowledge Infrastructure, Chinese Scientific Journal Database, Chinese Biomedical Literature Database, and Wanfang Database to identify randomized controlled trials (RCTs) in which hypertensive patients were treated with BLT or BLT plus antihypertensive drugs (BPAD) against placebo, no treatment or antihypertensive drugs. The Cochrane Risk Assessment Tool was used to assess the methodological quality of trials. The Review Manager 5.3 software was used for meta-analysis. RESULTS: A total of 7 RCTs with 637 hypertensive patients from 1989 to 2017 were identified. Compared with antihypertensive drugs, blood pressure was significantly reduced by BLT (RR=1.21, 95% CI: 1.01 to 1.44, P=0.03; heterogeneity: P=0.06, I=60%) and BPAD (RR=1.25, 95% CI, 1.02 to 1.53, P=0.03; heterogeneity: P= 0.01, I=71%). Moreover, a significant improvement in Chinese medicine syndrome by BLT (RR=1.32; 95% CI: 1.14 to 1.53, P=0.0002; heterogeneity: P=0.53, I=0%) and BPAD (RR=1.47; 95% CI: 1.06 to 2.04, P=0.02; heterogeneity: P=0.13, I=56%) was identified. The reported adverse effects were well tolerated. CONCLUSION Although some positive findings were identified, no definite conclusions regarding the efficacy and safety of BLT as complementary and alternative approach for treatment of hypertension could be drew due to the generally poor methodological design, significant heterogeneity, and insufficient clinical data. Further rigorously designed trials are warranted to confirm the results.
Adult ; Aged ; Aged, 80 and over ; Antihypertensive Agents ; therapeutic use ; Blood Pressure ; drug effects ; Bloodletting ; Combined Modality Therapy ; Humans ; Hypertension ; drug therapy ; physiopathology ; therapy ; Medicine, Chinese Traditional ; Middle Aged ; Randomized Controlled Trials as Topic ; Syndrome ; Treatment Outcome

Activation of peripheral respiratory chemoreceptors provokes respiratory and cardiovascular reflexes, providing a novel understanding of pathogenic mechanism of hypertension. Here we hypothesize that activation of peripheral respiratory chemoreceptors by hypoxia causes enhanced cardiorespiratory activity in conscious spontaneously hypertensive rats (SHRs). Using whole body plethysmography in combination with radio telemetry, pulmonary ventilation, arterial blood pressure and heart rate were examined in SHRs and Wistar-Kyoto (WKY) rats. We found that exposure to hypoxia induced greater increases in tidal volume and minute ventilation volume in SHRs compared to WKY rats. In addition, hypoxia caused a robust increase in arterial blood pressure and heart rate in SHRs relative to WKY counterparts. After carotid body denervation, the hypoxic ventilatory response was significantly decreased in both SHRs and WKY rats, but without significant difference between the two strains; moreover, the differences of arterial blood pressure and heart rate changes during hypoxic exposure were statistically insignificant between SHRs and WKY rats. It is concluded that hypoxia remarkably potentiates cardiorespiratory activity in the SHRs, suggesting an enhanced sensitivity of carotid bodies to hypoxia.
Animals ; Blood Pressure ; Heart Rate ; Hypertension ; physiopathology ; Hypoxia ; physiopathology ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY

BackgroundPrevious studies have shown that hypertension is an important factor contributing to the occurrence and progression of diabetic kidney damage. However, the relationship between the patterns of blood pressure (BP) trajectory and kidney damage in the diabetic population remains unclear. This prospective study investigated the effect of long-term systolic BP (SBP) trajectory on kidney damage in the diabetic population based on an 8-year follow-up community-based cohort.

MethodsThis study included 4556 diabetic participants among 101,510 participants. BP, estimated glomerular filtration rate (eGFR), and urinary protein were measured every 2 years from 2006 to 2014. SBP trajectory was identified by the censored normal modeling. Five discrete SBP trajectories were identified according to SBP range and the changing pattern over time. Kidney damage was evaluated through eGFR and urinary protein value. A multivariate logistic regression model was used to analyze the influence of different SBP trajectory groups on kidney damage.

ResultsWe identified five discrete SBP trajectories: low-stable group (n = 864), moderate-stable group (n = 1980), moderate increasing group (n = 609), elevated decreasing group, (n = 679), and elevated stable group (n = 424). The detection rate of kidney damage in the low-stable group (SBP: 118-124 mmHg) was the lowest among the five groups. The detection rate of each kidney damage index was higher in the elevated stable group (SBP: 159-172 mmHg) compared with the low-stable group. For details, the gap was 4.14 (11.6% vs. 2.8%) in eGFR <60 ml·min·1.73 m and 3.66 (17.2% vs. 4.7%), 3.38 (25.0% vs. 7.4%), and 1.8 (10.6% vs. 5.9%) times in positive urinary protein, eGFR <60 ml·min·1.73 m and/or positive urinary protein, and eGFR decline ≥30%, respectively (P < 0.01).

ConclusionAn elevated stable SBP trajectory is an independent risk factor for kidney damage in the diabetic population.

Asian Continental Ancestry Group ; Blood Pressure ; physiology ; Female ; Glomerular Filtration Rate ; physiology ; Humans ; Hypertension ; physiopathology ; Logistic Models ; Male ; Prospective Studies ; Risk Factors

PURPOSE: Impaired left ventricular (LV) global longitudinal strain (GLS) and the presence of microalbuminuria indicate early cardiac and renal dysfunction. We aimed to determine the relationships among 24-h ambulatory blood pressure (BP) variables, LV GLS, and urine albumin creatinine ratio (UACR) in hypertensive patients. MATERIALS AND METHODS: A total of 130 hypertensive patients (mean age 53 years; 59 men) underwent 24-h ambulatory BP monitoring, measurements of peripheral and central BPs, and transthoracic echocardiography. Patients with apparent LV systolic dysfunction (LV ejection fraction < 50%) or chronic kidney disease were not included. LV GLS was calculated using two-dimensional speckle tracking, and UACR was analyzed from spot urine samples. RESULTS: In simple correlation analysis, LV GLS showed the most significant correlation with mean daytime diastolic BP (DBP) (r=0.427, p < 0.001) among the various BP variables analyzed. UACR revealed a significant correlation only with night-time mean systolic BP (SBP) (r=0.253, p=0.019). In multiple regression analysis, daytime mean DBP and night-time mean SBP were independent determinants for LV GLS (β=0.35, p=0.028) and log UACR (β=0.49, p=0.007), respectively, after controlling for confounding factors. Daytime mean DBP showed better diagnostic performance for impaired LV GLS than did peripheral or central DBPs, which were not diagnostic. Night-time mean SBP showed satisfactory diagnostic performance for microalbuminuria. CONCLUSION: There are different associations for daytime and night-time BP with early cardiac and renal dysfunction. Ambulatory BP monitoring provides more relevant BP parameters than do peripheral or central BPs regarding early cardiac and renal dysfunction in hypertensive patients.
Blood Pressure/physiology ; *Blood Pressure Monitoring, Ambulatory ; Echocardiography ; Female ; Heart/*physiopathology ; Humans ; Hypertension/diagnostic imaging/*physiopathology ; Kidney/*physiopathology ; Kidney Function Tests ; Male ; Middle Aged ; Regression Analysis ; Systole/physiology ; Ventricular Dysfunction, Left/physiopathology ; Ventricular Function, Left/physiology

BACKGROUND: Age-related low-grade inflammation causing endothelial disruption influences sarcopenia, hypertension, and atherosclerosis. We reported previously that maintenance of muscle strength in elderly hypertensive men with high platelet levels is positively associated with subclinical atherosclerosis but not in those with low platelet levels. Since reduced tongue pressure is related to sarcopenia, tongue pressure may be associated with subclinical carotid atherosclerosis in hypertensive elderly subjects, and platelet levels may function as an indicator of the association between tongue pressure and subclinical carotid atherosclerosis. METHODS: We conducted a cross-sectional study of 342 hypertensive elderly Japanese men aged 60-89 who participated in an annual health check-up in 2015 and 2016. Subclinical carotid atherosclerosis was defined as a common carotid intima-media thickness (CIMT) of 1.1 mm or more. RESULTS: In the overall study population, 171 subjects demonstrated low platelets (< 21.4 × 10/μL). Tongue pressure was significantly inversely associated with subclinical carotid atherosclerosis in these subjects, but not in subjects with high platelets. The known cardiovascular risk factor adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of subclinical carotid atherosclerosis for a 1 standard deviation (SD) increment in tongue pressure (10.4 kPa) were 0.54 (0.35, 0.85) and 1.31 (0.87, 1.96), respectively. CONCLUSION Tongue pressure is inversely associated with subclinical carotid atherosclerosis in hypertensive elderly men with low platelet levels, but not in those with high levels. This finding may thus constitute an efficient tool for clarifying the background mechanism of age-related diseases such as sarcopenia, hypertension, and atherosclerosis.
Aged ; Aged, 80 and over ; Aging ; blood ; physiology ; Carotid Artery Diseases ; blood ; physiopathology ; Carotid Intima-Media Thickness ; Confidence Intervals ; Cross-Sectional Studies ; Humans ; Hypertension ; blood ; physiopathology ; Japan ; Male ; Middle Aged ; Odds Ratio ; Platelet Count ; Pressure ; Risk Factors ; Tongue ; physiology

Fructose intake has increased dramatically over the past century and the upward trend has continued until recently. Increasing evidence suggests that the excessive intake of fructose induces salt-sensitive hypertension. While the underlying mechanism is complex, the kidney likely plays a major role. This review will highlight recent advances in the renal mechanisms of fructose-induced salt-sensitive hypertension, including (pro)renin receptor-dependent activation of intrarenal renin-angiotensin system, increased nephron Na transport activity via sodium/hydrogen exchanger 3 and Na/K/2Cl cotransporter, increased renal uric acid production, decreased renal nitric oxide production, and increased renal reactive oxygen species production, and suggest actions based on these mechanisms that have therapeutic implications.
Blood Pressure ; Fructose ; adverse effects ; Humans ; Hypertension ; chemically induced ; physiopathology ; Kidney ; physiopathology ; Nitric Oxide ; metabolism ; Reactive Oxygen Species ; metabolism ; Renin-Angiotensin System ; Sodium Chloride, Dietary ; adverse effects ; Sodium-Hydrogen Exchanger 3 ; metabolism ; Uric Acid ; metabolism

Objective: To investigate the relationship between the maximum blood pressure fluctuation within 24 hours after admission and the prognosis at discharge. Methods: The patients with ischemic stroke admitted in Department of Neurology of the First Affiliated Hospital of Harbin Medical University within 24 hours after onset were consecutively selected from April 2016 to March 2017. The patients were grouped according to the diagnostic criteria of hypertension. Ambulatory blood pressure of the patients within 24 hours after admission were measured with bedside monitors and baseline data were collected. The patients were scored by NIHSS at discharge. The relationships between the maximum values of systolic blood pressure (SBP) or diastolic blood pressure (DBP) and the prognosis at discharge were analyzed. Results: A total of 521 patients with acute ischemic stroke were enrolled. They were divided into normal blood pressure group (82 cases) and hypertension group(439 cases). In normal blood pressure group, the maximum values of SBP and DBP were all in normal distribution (P>0.05). The maximum value of SBP fluctuation was set at 146.6 mmHg. After adjustment for potential confounders, the OR for poor prognosis at discharge in patients with SBP fluctuation ≥146.6 mmHg was 2.669 (95%CI: 0.594-11.992) compared with those with SBP fluctuation <146.6 mmHg. The maximum value of DBP fluctuation was set at 90.0 mmHg, and the adjusted OR for poor prognosis at discharge in patients with DBP fluctuation ≥90.0 mmHg was 0.416 (95%CI: 0.087-1.992) compared with those with DBP fluctuation <90.0 mmHg. In hypertension group, the maximum values of SBP and DBP were not in normal distribution (P<0.05). The maximum value of SBP fluctuation was set at median 171.0 mmHg. After adjustment for the confounders, the greater the maximum of SBP, the greater the risk of poor prognosis at discharge was, the OR was 1.636 (95%CI: 1.014-2.641). The maximum value of DBP fluctuation was set at median 98.0 mmHg. After adjustment for the confounders, the greater the maximum of DBP, the greater the risk of poor prognosis at discharge was, the OR was 1.645 (95%CI: 1.003-2.697). Conclusion: In acute ischemic stroke patients with normal blood pressure at admission, the maximum values of SBP and DBP within 24 hours after admission had no relationship with prognosis at discharge. In acute ischemic stroke patients with hypertension at admission, the maximum values of SBP and DBP within 24 hours after admission were associated with poor prognosis at discharge.
Adult ; Blood Pressure/physiology* ; Blood Pressure Monitoring, Ambulatory ; Brain Ischemia/physiopathology* ; Hospitals ; Humans ; Hypertension/physiopathology* ; Outcome Assessment, Health Care ; Patient Admission ; Patient Discharge ; Prognosis ; Risk ; Stroke/physiopathology* ; Time-to-Treatment