bluuebunny/crossref_metadata_2025 huggingface dataset:
INPATIENT HYPERTENSION PREDICTS AMBULATORY HYPERTENSION IN PREVIOUSLY NORMOTENSIVE PATIENTS
Authors: Zanuzzi Matías Gabriel , Álvarez José Ignacio , Garay Sofía Belén , Peñaranda Gabriela Estefan , Romero César Andrés
Published: April 2021

Objective:

To determine the prevalence of uncontrolled hypertension (HTN) in hospitalized patients.

To establish if uncontrolled hypertension during hospitalization impacts on the outcomes of the hospitalization.

To evaluate if in-hospital hypertension is a risk factor for diagnosis of ambulatory hypertension.

Design and method:

Retrospective, analytical and cohort study. All patients admitted to the general inpatient ward of the Hospital Privado Universitario de Córdoba (Argentina) between March 1st and April 30th, 2016 were analyzed. Blood Pressure (BP) values were recorded at admission, all measurements during the hospital stay, at discharge, at 1 month and 3 years after discharge. Inpatient HTN was defined through two different methods: (a) at least two BP measurements greater or equal to 140/90 mmHg on at least two different days; (b) average of all measurements during hospitalization greater or equal to 130/80 mmHg.

Results:

1073 patients were included. Mean age was 56.2 (18 - 95) years. 50.3% were female. 46.6% had previous HTN diagnosis, 88.4% were under treatment. The prevalence of the inpatient hypertension was 59.1% with method (a) and 27.5% with method (b). 62.9% did not receive specific treatment during hospitalization. Apparent HTN triggers were present in 22.8% of the patients. Patients with HTN during hospitalization had a longer stay (6.0 ± 5.1 vs. 4.7 ± 6.2 days; p < 0.01), doubling the risk of prolonged hospitalization (OR 1.77; [1.37 - 2.29]; p < 0.01). Among patients without history of HTN prior to hospitalization, having inhospital hypertension was associated with a higher risk of presenting outpatient hypertension at month (method a= RR: 3.38; [0.60 - 19.16]; p = 0.15 and method b = RR: 7.5; [1.32 - 42.5]; p = 0.03) and 3 years after hospitalization (method a = RR: 3.25; [1.15 - 9.20]; p: 0.02 and method b = RR: 3.34; [1.27 - 8.77]; p = 0.02).

Conclusions:

Despite the high prevalence of HTN during hospitalization most patients dońt receive specific treatment. The development of HTN is not conditioned only by factors inherent to hospitalization. Inpatient HTN is associated with a longer stay and predicts ambulatory HTN.
METABOLIC SYNDROME AMONG HYPERTENSIVE PATIENTS: PREVALENCE AND ASSOCIATED RISK FACTORS AMONG ADULTS OF SOUTHERN RAJASTHAN, INDIA
Authors: Verma Anjana , Patyal Ashish
Published: April 2021

Objective:

The present study was designed to estimate the prevalence of metabolic syndrome and evaluate other associated risk factors among hypertensive adults of the southern part of Rajasthan, India.

Design and method:

A total of 2100 hypertensive patients were interviewed using a pretested and validated questionnaire about lifestyle practices and medical history. The diagnosis of Metabolic Syndrome (MS) was done using National Cholesterol Education Program – Adult Treatment Panel III criteria with an anthropometric modification of waist circumference (WC) value that is specifically applicable to South Asians. Hypertension (HTN) was diagnosed with BP over 130 and/or > 85 mm Hg, abdominal obesity (AO) according to waist circumstance (WC) > 90/80 cm men/women, hypertriglyceridemia (HTG) > 150 mg/dl, hyperglycemia > 110 mg/dl, decreased HDL < 40/50 mg/dl for men/women. Biochemical parameters (lipids and glucose) were measured using sphectrometry on COBAS (ROCHE) equipment. All calculations and statistical analyzes are processed by the SPSS 21.0.

Results:

The study subjects were 58% males and 42% females, with a mean age of 46.21 ± 9.40 years. Abdominal obesity was found in 57.3%, HTG 31.8%, hyperglycemia 32.6%, decreased HDL 29.2%, MS 31.4%. Diabetes prevalence was found to be 21.2% including 17% of known cases and 4.2% of new cases. Regarding the risk factors, 28.7 % were tobacco smokers; Physical inactivity 49%, more frequent in men than women (p = 0.04); Abdominal obesity was significantly higher in women; diabetes was associated with abdominal obesity and dyslipidemia in 59% of cases; 67.8% of subjects had at least three associated risk factors.

Conclusions:

Indian subcontinent has highest rates of CVDs worldwide. This study reveals high prevalence of metabolic syndrome as well as other risk factors. It is necessary to do nation wide surveys to formulate effective preventive strategies.
EPIDEMIOLOGY OF HYPERTENSION IN NORTH INDIA: A COMPREHENSIVE STUDY OF ANTHROPOMETRIC, DEMOGRAPHIC AND SOCIO-ECONOMIC FACTORS AFFECTING HYPERTENSIVE PATIENTS
Authors: Rastogi Smriti , Verma Narsingh , Patel Munnalal
Published: April 2021

Objective:

To find out relation & effect of various anthropometric, demographic and socio-economic factors influencing blood pressure.

Design and method:

800 secondary hypertensives (18–60 years) from Medicine OPD, KGMU, Lucknow were studied for anthropometric measurements, 3 readings of blood pressure were taken in each arm (right and left) from OMRON HEM CR-24 BP monitor and average was calculated. Patients with Systolic Blood Pressure (SBP) greater than or equal to one hundred and forty mm Hg, Diastolic Blood Pressure (DBP) greater than or equal to 90 mmHg were enrolled. A sociodemographic, medical history proforma and Goldberg questionnaire (for depression) was filled. Place of residence (low/high population density), village/city, colony/individual house/apartment/multi storeyed building, park nearby/not, living with family/alone, vegetarian/ not, meal timings, alcohol & or tobacco intake, physical activity, meditation/yoga, office hours, self- driving/not, marital status, time spent on social media, exposure to artificial light, online gaming, frequency of fasting, pets, leisure hours,per month income, medical history, duration and quality of sleep was recorded.

Results:

65 % hypertensive males, hypertensive females 35% 96.6 % (773 out of 800) of the secondary hypertensives were found to be living with their families and only 27 patients were living alone. 60 % of 800 secondary hypertensives that is 300 patients were found to living in a joint family set up whereas40 percent were living only with their immediate family.

All respondents were married, 23% were widowed. Age > 46 years for males > 52.4 years for females BMI > 21.3 for males and > 26.4 for females Male gender showed a predilection < 5 hrs / week of physical activity (walking) Living in individual houses Education level (less than class 10) were significantly associated with hypertension.

Conclusions:

Hypertension is significantly associated with the above mentioned socioeconomic factors.
BLOOD PRESSURE CONTROL IN A HIGH-COMPLEXITY OUTPATIENT SERVICE WAS LESS THAN ADHERENCE TO ANTIHYPERTENSIVE TREATMENT
Authors: Guimaraes Mayra Cristina Luz Pádua , Coelho Juliana Chaves , Da Silva Giovanio Vieira , Pierin Angela
Published: April 2021

Objective:

To evaluate the blood pressure control, adherence to antihypertensive treatment and associated variables.

Design and method:

A cross-sectional study was performed in a hypertension outpatient clinic from a Hospital in São Paulo, Brazil. Inclusion criteria were: age over 18 years old, in treatment for at least six months and also that accepted to participate signing the Informed Consent Form. Patients diagnosed with secondary hypertension, pregnant and unable to answer the interview were excluded. The sample calculation based on 60% of control rate and 5% of significance level was 253 participants. The blood pressure control was systolic blood pressure < 140 and diastolic blood pressure < 90 mmHg. The adherence to treatment was assessed by Morisky MMAS-8. Biosocial data, risk factors, habits, lifestyles, anthropometric measurements, comorbidities and psycho-emotional characteristics were evaluated. Multivariate analysis was performed by the Logistic Regression and the significance level was <0.05.

Results:

The blood pressure control was 69.2% and 82.2% had a high adherence to treatment. The characteristics of hypertensive patients were: 65.0 (13.3) years, 61.7% were female, 63.2% were white, 52.8% were married, 44.3% had completed high school studies, body mass index 29.5 (5.3) Kg/m2 (81.4% overweight or obesity), 47.4% had a low socio economic classification, 55.7% had never smoked, 60% hadn’t drunk alcoholic beverage currently, 84.5% hadn’t had common mental disorders, 39.9% had physical activity irregularly and 8.0 (4.0) number of drugs in use. The main comorbidities were: Dyslipidemia (71.5%), Diabetes Mellitus (40.7%), Chronic Kidney Disease (19%), Stroke (8.7%), Coronary Insufficiency (13.4%). The systolic blood pressure was 138.6 (12.1) mmHg and diastolic was 80.8 (7.2) mmHg. The most used antihypertensive drugs were: diuretics (78.3%), calcium channel blockers (68.8%), AT1 receptor blockers (61.7%), beta-blocker adrenergic inhibitors (50.2 %) and angiotensin-converting enzyme inhibitor (30.4%). The associated variables to blood pressure control were: married marital status (OR 2.3; IC95%:1.34 – 4.28), calcium channel blockers (OR 0.4; IC95%: 0.19–0.92) and number of antihypertensive drugs in use (OR 0.78; IC95%:0.66–0.92).

Conclusions:

The blood pressure control were more elevated than data from majority of Brazilian studies, although not coincident to the adherence to the treatment evaluated.
CAFFEIC ACID AMELIORATES ANGIOTENSIN II-INDUCED INCREASE IN BLOOD PRESSURE BY ACTIVATING VASCULAR SARCO-/ENDOPLASMIC RETICULUM CA-ATPASE2A
Authors: Wu Hao , Zhang Liting , Gao Peng , Liu Daoyan , Zhu Zhiming
Published: April 2021

Objective:

Many studies have focused on reporting the beneficial effect of consumption coffee or caffeine on cardiovascular disease. However, caffeic acid, a component of coffee, which has a completely different structure from caffeine, was rarely studied in cardiovascular metabolic diseases. In this study, we investigated the effect of caffeic acid on vascular function and blood pressure of mice.

Design and method:

Tension of endothelium-free mesenteric arteries from 8-week-old male wild-type (WT) mice was measured using wire myograph. Cytoplasmic Ca2+ and sarcoplasmic reticulum (SR) Ca2+ were measured from primary vascular smooth muscle cells (VSMCs) using fura-2AM and mag-fura-2AM, respectively. Molecular docking was performed by AutoDock to determine the binding force and sites of caffeic acid with sarco-/endoplasmic reticulum Ca-ATPase (SERCA, a channel transporting Ca2+ from the cytosol into the SR lumen. PDB: 2YFY). 8-week-old male SERCA2a knockout mice and WT littermates were surgically implanted with mini-osmotic pumps filled with angiotensin II (Ang II) solutions. Then these mice were fed with normal diet or 0.05% caffeic acids in drinking water for 8 weeks. The tail-cuff blood pressure (BP) and 24-hour ambulatory BP were measured.

Results:

First, we found that caffeic acid relaxed mesenteric artery pre-contracted with norepinephrine (NE) with half-effective dose of 26.7uM. Furthermore, pre-treatment with 50uM caffeic acid for 5 min completely smoothed NE-induced vasoconstriction. Specifically, we found that caffeic acid reduced intracellular Ca2+ in a concentration-dependent manner as well as resisted the increase of intracellular Ca2+ induced by thapsigargin, a SERCA inhibitor, whereas caffeic acid increased SR Ca2+ uptake. Molecular docking revealed caffeic acid binds to SERCA to form strong hydrogen bonds at ASN-359, TYR-389, ARG-604 and ASP-738. Eventually, we found that compared with the normal diet group, the intervention of caffeic acid significantly attenuated AngII-induced increases of tail BP and ambulatory BP in mice, but the hypotensive effect of caffeic acid disappeared in SERCA2a knockout mice.

Conclusions:

These results suggest that caffeic acid has a beneficial effect on vascular function and blood pressure by activating SERCA2a on VSMCs. Consumption coffee or caffeic acid may be an effective lifestyle to prevent and treat hypertension.
BLOOD PRESSURE CONTROL-RATES THROUGH MONOTHERAPY WITH FOUR DIFFERENT ANTIHYPERTENSIVE AGENTS IN TREATMENT-NAÏVE PATIENTS WITH ARTERIAL HYPERTENSION
Authors: Vischer Annina , Socrates Thenral , Mayr Michael , Haschke Manuel , Burkard Thilo
Published: April 2021

Objective:

Four different antihypertensive agent classes are equivalently recommended in the guidelines for first-line treatment of arterial hypertension (AHT). However, it is unclear, if one of these agents is more potent than the others to reach blood pressure (BP) control. We sought to compare response rates and BP control in these four classes.

Design and method:

Patients with newly diagnosed grade 1 or 2 AHT on 24h-BP measurements (ABPM) were randomized in a 1:1:1:1 fashion to either perindopril (ACE), olmesartan (ARB), amlodipin (CCB) or hydrochlorothiazide (HCT). ABPM were checked at baseline (BL), after 4 weeks of half dose (TP1) and after 4 weeks of full dose (TP2), if BP control was not reached after TP1. Patients were classified as controlled if mean BP was < 130/80 mmHg, awake BP < 135/85 mmHg and night BP < 120/70 mmHg.

Results:

80 patients were randomized: 20 (25.0%) to ACE, 20 (25.0%) to ARB, 21 (26.3%) to CCB, and 19 (23.8%) to HCT. Mean age was 48 (±14) years, mean BMI 26.5 (±3.7) kg/m2. Mean 24 h systolic BP (sBP) was 141.8 (± 9.1) mmHg, diastolic BP (dBP) 87.8 (± 7.6) mmHg (Table). Mean decrease from BL to TP1 was -5.8 (± 10.9) and -2.7 (± 5.6) mmHg, from BL to TP2 -11.6 (± 11.2) and -5.6 (± 6.7) mmHg, from TP1 to TP2 -5.8 (± 12.0) and -2.8 (± 5.4) mmHg, for mean 24 h sBP and dBP, respectively. After TP1, 21 patients (26.3%) had a controlled BP overall (Figure). After TP2, the number of controlled patients increased to 24 patients (30.0%, p = 0.250, Figure). Control rates were significantly lower for HCT in comparison to the other agents for diastolic values after TP1 (p = 0.013) and after TP1 and TP2 (p = 0.003).

Conclusions:

Half dose of the most common antihypertensive treatments lead to BP control in 26% of patients with grade 1 or 2 AHT. Control rates were not significantly improved when increasing to full dose. HCT was the least effective, whereas ACE, ARB and CCB were comparably effective.
USE OF ALTERNATIVE MEDICINE IN A SAMPLE OF PATIENTS IN A CARDIOVASCULAR PREVENTION CLINIC
Authors: Spagnuolo Vitaliano , Pulicanò Martina , Maretta Alessia
Published: April 2021

Objective:

Alternative medicine can play a role in improving the health and well-being of people and can be integrated with traditional medicine. It is often self-prescribed and it can expose to potential risks from drug interactions with conventional medicine drugs.

Design and method:

We evaluated, in a group of patients in a clinic dedicated to prevention for cardiovascular diseases, the use of alternative medicines in the last year.

We enrolled the first hundred patients, aged over 50, of outpatient visit to Cardiovascular Prevention Clinic (Lipid Center Cosenza). All hundred patients were given a questionnaire consisting of five simplified questions (validated questionnaire proposed in an AARP/NCAAM study).

Results:

Of the 100 patients, 55 were females. The average age was 66.6 ± 8.45 years; 68.2 ± 6.4 for females and 64.7 ± 10for males. Twenty-five of them reported the use, in the last year, of one of the alternative medicines recognized by our legal system. Osteopathy and chiropractic were the most used (15 patients), posturology (5 patients), herbs (5 patients). Females were more prone to use alternative medicines (20 vs 5). The most frequently given motivation to use alternative medicines was to solve a certain pathological condition (77%) rather than prevent a disease. Regarding to full awareness in carrying out alternative therapy, 15 patients out of 25 fully knew the indication for use before starting it, and the same fifteen had received precise indications from their doctor.

Seventy-five were already being treated with at least one drug before enrollment (average 2.35 ± 1.9). Of the 25 patients who used alternative medicines, all took at least two drugs (average 3.6 ± 1.2).

Conclusions:

The fact that they have taken substances without having informed a healthcare professional has potential for risk, given the possible interaction between medicines also in the field of complementary medicine. Alternative medicine is widely used in our reality, but often without the patient informing the doctor. Better management of counseling is therefore necessary to improve the indication and safety of the use of complementary medicines.
METOPROLOL COMPARED TO AMLODIPINE IMPAIRS MITOCHONDRIAL FUNCTION IN FOREARM SKIN IN HYPERTENSIVE PATIENTS
Authors: Pawlak-Chomicka Regina , Uruski Pawel , Krauze Tomasz , Markowska Malgorzata , Tykarski Andrzej , Guzik Przemyslaw
Published: April 2021

Objective:

If oxygen is available, then mitochondria oxidase the reduced form of nicotinamide adenine dinucleotide (NADH) and produce energy. Oxygen delivery to mitochondria in skin cells depends on the function of microvascular circulation. Antihypertensive medications can modify both energy metabolism (e.g. gain of body weight) and microvascular function (cold fingers and toes). In this prospective study, we compared the effects of amlodipine vs metoprolol on the skin content of NADH in hypertensive patients.

Design and method:

Patients with newly diagnosed hypertension were randomly allocated to the six-week treatment with either 5 mg of amlodipine (20 patients) or 25 mg of metoprolol (17 patients) once a day. The 460-nm forearm skin fluorescence measured the skin mitochondrial content of NADH at rest, during transient 100-second ischaemia (by occlusion of the brachial artery with the inflated arm blood pressure cuff), and the following reperfusion. This measurement was made before and after the treatment initiation.

Results:

Hypotensive effects of both treatment were comparable after the six-week therapy. For NADH, amlodipine showed no significant change in the 460-nm fluorescence at rest (791.6 ± 281.1 to 733.7 ± 261.9 [kU] (p = 0.119), during ischemia (850.2 ± 292.2 to 805.6 ± 294.8 [kU] (p = 0.307), and reperfusion (662.3 ± 228.4 to 624.1 ± 225.0 [kU] (p = 0.210). In contrast, treatment with metoprolol significantly increased the 460-nm fluorescence at rest (678.2 ± 284.0 to 797.3 ± 247.0 [kU] (p < 0.01), during ischemia (736.5 ± 302.1 to 859.7 ± 264.9 [kU] (p < 0.01), and reperfusion (571.5 ± 243.2 to 662.2 ± 204.7 [kU] (p < 0.01).

Conclusions:

Metoprolol significantly impairs the function of skin mitochondria, causing a significant increase in the NADH content. In contrast, amlodipine shows neutral effects on this function.
ANTI-HYPERTENSIVE EFFECT OF THE DIPEPTIDE, TYROSYL-PROLINE, IN RVLM; A MICROINJECTION STUDY
Authors: Zahid Hasan Md. , Fujikawa Koichi , Ohara Hiroki , Okamoto Kenji , Nabika Toru
Published: April 2021

Objective:

Oligo-peptides were shown to have various physiological effects in-vivo. In this study, we evaluated antihypertensive activity of a dipeptide, tyrosyl-proline (YP), which was found in fermented milk at high concentration.

Design and method:

To evaluate effects of YP in CNS, YP was micro-injected into the rostral ventrolateral medulla (RVLM), the nucleus in the brainstem regulating blood pressure (BP), and changes in intra-arterial BP were monitored directly with a catheter inserted in the femoral artery in anesthetized rats. This study was supported by the Research Program on Development of Innovative Technology of the Bio-oriented Technology Research Advancement Institution, NARO.

Results:

YP microinjection into RVLM reduced BP in a dose-dependent manner. BP reduction at 100 pmole of YP was 41 ± 3 mmHg in SHRSP, which was as strong as that of LVY and IPP, both of which were known to have a potent anti-hypertensive effect. BP decrease was much smaller in WKY (7 ± 2 mmHg). Different sequences of dipeptide composed of tyrosine and proline (PY, YY and PP) showed much less effect on BP, excluding a possibility that the effect of YP on BP was non-specific. Naloxone (a non-specific inhibitor of opioid receptors) and nor-binaltorphimine (a selective inhibitor of kappa opioid receptor) antagonized the effect of YP, whereas naltrindole (a selective inhibitor of delta opioid receptor) failed to block it. This result implied that the effect of YP in RVLM was mediated by kappa opioid receptor.

Conclusions:

YP might play an important role in regulation of BP in RVLM through opioid receptors.
CHANGES IN MUSCLE-SPECIFIC MICRORNAS ACCOMPANY TERMINAL STAGES OF MONOCROTALINE-INDUCED PULMONARY HYPERTENSION IN RAT
Authors: Kmecova Zuzana , Veteskova Jana , Zirova Katarina , Pivackova Lenka Bies , Doka Gabriel , Malikova Eva , Krenek Peter , Passakova Nina , Paulis Ludovit , Luknar Milan , Goncalvesova Eva , Klimas Jan
Published: April 2021

Objective:

Importance of muscle-specific microRNAs (miR-1/miR-133a/miR-208/miR-499) has been identified in various cardiovascular pathologies, including their potential of being biomarkers in these diseases. Pulmonary arterial hypertension (PAH) is an incurable disease progressing into right ventricular (RV) failure as the leading cause of death. Here, we hypothesised that muscle-specific microRNAs influence RV damage in PAH and their plasma levels might be used also as indicators of disease severity.

Design and method:

12-weeks old male Wistar rats were administered either monocrotaline (MCT group) or vehicle (CON group) and the animals were sacrificed 4 weeks after this treatment. Certain animals from MCT group, in which the condition of pulmonary hypertension (PH) developed more severely, were terminated prematurely (ptMCT group), since they displayed signs of serious clinical worsening and so represented the terminal stage of PH. Additionally, plasma samples of patients diagnosed with PAH were obtained from a PAH referral centre. Expression of microRNAs, both in rats and humans, was determined by RT-qPCR.

Results:

Fulton index of MCT and ptMCT animals was gradually increased by 47% (p < 0.05 vs CON) and by 110% (p < 0.05 vs CON and MCT) respectively. Expression of muscle-specific microRNAs in RV was not significantly altered in MCT group, but we noted decrease in ptMCT group (-52% for miR-1, -61% for miR-133a, -64% for miR-208, -57% for miR-499 vs CON, all p < 0.05). In human plasma samples, only miR-1 and miR-133a expressions were reliably determinable by RT-qPCR, nevertheless, we noted no significant correlations with mean pulmonary arterial pressure, pulmonary vascular resistance, RV cardiac output or NT-proBNP levels.

Conclusions:

The decrease of muscle-specific microRNAs in ptMCT group suggests that they might not be responsible for RV modifications in earlier stages of developed PH, but their downregulation in RV tissue mirrors the severity of terminal stages of this experimental model. On the other hand, based on our results, the use of muscle-specific microRNAs as clinical biomarkers of PAH remains elusive and the attention should be directed to other miRNA candidates.
A HIGH SALT DIET ALTERS THE DAILY RHYTHM OF BLOOD PRESSURE IN C57BL6/J MICE
Authors: Ivy Jessica , Ralph Ailsa , Costello Hannah , Celine Grenier , Stewart Kevin , Dhaun Neeraj , Bailey Matthew
Published: April 2021

Objective:

Abnormal blood pressure (BP) rhythms precede and predict cardiovascular disease and are often linked with salt-sensitivity. The mechanisms underlying these rhythms are unknown. High dietary salt intake can cause phase shifts in the intrinsic circadian clocks within peripheral organs but the implications for BP rhythm are unclear. We investigated the effect of a high salt diet on the rhythms of BP, heart rate (HR) and activity.

Design and method:

BP was monitored by radiotelemetry in male C57BL6/J mice. After 1 week of 0.25% Na+ chow (baseline), mice received 3% Na+ diet for 3 weeks followed by 0.25% Na+ for a further 2 weeks (Na+ washout). Systolic BP (SBP), HR and activity data was analysed by cosinor analysis. Sympathetic nervous system activity was estimated by measuring 12 h urinary catecholamine spillover and plasma aldosterone was measured following a week of 3% Na+ diet.

Results:

Mesor (circadian mean) SBP increased by 7mmHg after week 1 of 3% Na+ diet. This was maintained over 3 weeks but reduced to baseline after Na+ washout. BP amplitude increased from 9mmHg (baseline) to 14mmHg within 1 week of 3% Na+ feeding. This was maintained for the 3 weeks of 3% Na+ but reduced to 8mmHg following Na+ washout. This reflected elevated active-phase BP rather than enhanced dip in sleep-phase BP. A ∼4.5-hour phase delay in SBP was observed in the second week of 3% Na+ diet. HR mesor did not change throughout the experiment but amplitude was elevated at 3 weeks of 3% Na+. Activity amplitude increased during the first week of 3% Na+ intake but was not maintained at week 2. Plasma aldosterone was appropriately suppressed but day and night urinary adrenaline levels were increased after 1 week on 3% Na+ diet.

Conclusions:

C57BL6/J mice exhibit salt-sensitive BP. A 3% Na+ diet altered BP rhythm by increasing amplitude and inducing a modest phase shift. Further studies are needed to investigate the role of the sympathetic system and intrinsic molecular clocks in the induction of these rhythms. This may give insights into mechanisms underlying the relationship between salt-sensitivity and abnormal BP rhythms.
ECTOPIC TWEAKR EXPRESSION IN TYPE I FIBER OF STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS IS RELATED TO SLOW MUSCLE-SPECIFIC HYPOTROPHY THROUGH MURF1 OVEREXPRESSION
Authors: Inoue Takao , Hagiyama Man , Maenishi Osamu , Kimura Masatomo , Mizuguchi Nobuyuki , Mine Yoshihiro , Kimura Ryuichiro , Chikugo Takaaki , Itoh Tatsuki , Satou Takao , Ito Akihiko
Published: April 2021

Objective:

The maintenance of muscle strength and mass is important for body homeostasis. Stroke-prone spontaneously hypertensive rats (SHRSP) show significantly higher blood pressure and lower body weight than normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). In addition, blood pressure and body weight show an inverse correlation among the rats. We hypothesized that skeletal muscle hypotrophy in hypertensive rats is related to hypertension-related diseases and is useful as a therapeutic target for hypertension and hypertension-related diseases. We aimed to investigate the pathophysiological characteristics of muscle hypotrophy in SHRSP to determine the therapeutic target molecule(s).

Design and method:

First, the difference in skeletal muscles in the lower leg between WKY and SHRSP was evaluated mainly through weight/tibial length and histological analysis. Further experiments were carried out based on gene expression using microarray, protein expression, and immunohistochemistry analyses.

Results:

SHRSP had a significantly lower weight/tibial length in the soleus and gastrocnemius, but not in the plantaris and tibialis anterior. This suggests that muscles with a relatively high amount of slow muscle fiber (type I fiber) show hypotrophy. Histological analysis of the soleus, showing that type I fibers mainly decreased the fiber size, corresponded to the result of weight/tibial length. Microarray and protein expression analyses showed that the muscle-specific ubiquitin ligase, muscle RING finger 1 (MuRF1), but not atrogin-1, was highly expressed in the soleus, but not in the plantaris, in SHRSP. TNF-like weak inducer of apoptosis receptor (TWEAKR) was predicted as a MuRF1 up-regulator in the Ingenuity Pathway Analysis. There was no significant difference in TWEAKR expression level in the soleus between WKY and SHRSP. However, immunofluorescence revealed that WKY had only type II fiber staining, but SHRSP had both type I and II fiber staining.

Conclusions:

TWEAKR is a type II-specific receptor in the skeletal muscle. Ectopic TWEAKR expression in type I fibers of SHRSP is most likely involved in slow muscle-specific hypotrophy through MuRF1 overexpression. The TWEAKR-MuRF1 pathway may be a useful therapeutic target for slow muscle hypotrophy.
SEX DIFFERENCES IN RESPONSE TO STRESS IN MALE AND FEMALE HYPERTENSIVE SCHLAGER MICE
Authors: Gueguen Cindy , Jackson Kristy L. , Le-Pham Phuong-Nhan , Head Geoffrey A.
Published: April 2021

Objective:

The inbred hypertensive mouse strain (BPH/2) and a normotensive strain (BPN/3) are thought to be a neurogenic form of hypertension. The aim of the current study was to compare the cardiovascular characteristics of male and female hypertensive and normotensive mice to determine any sex differences in the underlying mechanisms.

Design and method:

12-week-old hypertensive BPH/2J and normotensive BPN/3J male and female mice were implanted with telemetry probes to record blood pressure (BP), heart rate and activity. Cardiovascular responses to restraint, dirty cage swap, feeding, enalaprilat and pentolinium were measured in conscious mice.

Results:

Mean, systolic, diastolic BP, heart rate and activity were similar in males and females but higher in BPH/2 than BPN/3 (n = 5–7). Day night differences in BP were 3 times higher in BPH/2 compared to BPN/3 (17 vs 6 mmHg respectively) but similar in male and female mice. The depressor responses to enalaprilat reduced BP by -11 ± 1 mmHg and was similar in both male strains but greater in female BPH/2 mice (-17 ± 1 mmHg). Blocking the sympathetic nervous system activity produced a 5-fold greater reduction in BP in male and female BPH/2 mice. The pressor response to restraint stress was higher in BPH/2 than BPN/3 but similar in the males and females of each strain. While the pressor response to dirty cage swap was greater in BPH/2 than BPN/3 mice, it was also greater in males than females. Treatment with a synthetic neurosteroid ganaxolone (5 mg/kg/day) for 2 weeks attenuated the pressor response to cage swap only in male BPH/2 mice and not in females. The percentage of time spent in a dark area compared to the light (indicating anxiety) was similar in males and females of both strains.

Conclusions:

While hypertension is similar in male and female BPH/2 mice the differential response to behavioral stress tests and their susceptibility of attenuation by ganaxolone in males and females suggests important differences in the central pathways controlling the adverse response to stress. Understanding these differences may be relevant to the higher cardiovascular risk observed in males.
A SELECTIVE UPREGULATION OF GABAA RECEPTOR SUBUNIT EXPRESSION IS ASSOCIATED WITH THE HYPOTENSIVE EFFECTS OF GANAXOLONE IN MALE HYPERTENSIVE SCHLAGER MICE
Authors: Gueguen Cindy , Le-Pham Phuong-Nhan , Jackson Kristy L , Paterson Madeleine R , Esler Murray , Marques Francine Z , Lambert Elisabeth , Head Geoffrey A
Published: April 2021

Objective:

Ganaxolone is a synthetic form of allopregnanolone, an allosteric modulator of gamma aminobutyric acid type A receptors (GABAAR). Allopregnanolone reduced blood pressure (BP) in male BPH/2J mice with neurogenic hypertension (Stevenson et al., 2017), which suggests that a lack of tonic inhibition in the forebrain mediates the hypertension. The hypotensive effect of allopregnanolone was associated with an upregulation of the GABAAR alpha4 and delta-subunit mRNA in the hypothalamus and medial amygdala of BPH/2J mice. The objective of this study was to investigate the temporal association of the antihypertensive effects of ganaxolone and the alteration in the different GABAAR subunits in the forebrain of BPH/2J mice.

Design and method:

12-week-old hypertensive BPH/2J and normotensive BPN/3J male mice were implanted with a telemetry probe to record BP and heart rate. Cardiovascular responses to stress tests and pentolinium were measured before and after administering vehicle or ganaxolone (5 mg/kg/day, subcutaneous minipumps) for 2 weeks. The mRNA expression of the GABAAR subunits was measured by real-time PCR 1 to 2 weeks after the beginning of the treatment in vehicle or ganaxolone-treated BPH/2J mice.

Results:

After 2 weeks, ganaxolone reduced BP by 10.7 mmHg (P < 0.001) in male BPH/2J mice and reduced the pressor responses during restraint (-8.2 mmHg, P < 0.001) and dirty-cage switch (-12.4 mmHg, P < 0.001) stresses compared with pre-treatment. One-week treatment with ganaxolone or vehicle had no effect on cardiovascular parameters on either strain. Ganaxolone-treated BPH/2J mice had increased mRNA expression of alpha4-subunit and showed a trend towards increased delta-subunit of hypothalamic GABAAR compared to vehicle-treated BPH/2J. None of these effects were seen at 1-week post-treatment and in BPN/3J mice.

Conclusions:

Ganaxolone reduced hypertension and the cardiovascular response to stress in male BPH/2J mice but only when upregulated alpha4 and delta-subunit mRNA expression of the GABAAR was observed. Therefore, it is likely that the main mechanism of the delayed antihypertensive effects of ganaxolone in neurogenic hypertensive mice is dependent on upregulation of specific GABAAR subunits.
ARYL HYDROCARBON RECEPTOR ANTAGONISTS - A NEW ENTRY IN ANTIHYPERTENSIVE ARMAMENTARIUM OF OBSTRUCTIVE SLEEP APNEA?
Authors: Pereira Sofia Azeredo , Coelho Nuno R. , Tomkiewcz Céline , Correia Maria João , Pimpao Antonio B. , Barouki Robert , Coumoul Xavier , Monteiro Emilia C
Published: April 2021

Objective:

To investigate aryl hydrocarbon receptor (AhR) metabolic circuitry as a druggable target in chronic intermittent hypoxia (CIH) induced hypertension (HTA).

Design and method:

This study was approved by Nova Medical School's Ethics Committee and followed national and international regulations. We used a rat model of CIH-induced HTA to disclose the hypothesis that the aryl hydrocarbon receptor (AHR) is activated by IH, once it shares the same binding partner of HIF-1alpha and promotes pro-oxidant, pro-inflammatory (NF-kB) and pro-fibrotic events in common with CIH. AhR activation was measured by the mRNA and protein levels of its hallmark target gene Cyp1a1. Blood pressure, heart rate and locomotor activity were measured daily by radiotelemetry. A CIH paradigm of 21% to 5% of O2, 5.6 cycles/h, 10.5 h/day was used in their inactive/sleep period.

Results:

Upon established hypertension (21 days exposure to IH), we observed an increase in Cyp1a1 mRNA (hallmark of AhR activation) in kidney cortex (6-fold), kidney medulla (3-fold) and liver (3-fold), but not in other tissues. Increased renal expression of Ahr and markers of inflammation (Rela), epithelial to mesenchymal transition markers, the rate-controlling step of gluconeogenesis, Pepck1, and members of HIF-pathway, namely, Hif-3alpha were also observed. The ratio kynurenin/tryptophan (inflammatory index) was also increased in the kidney. The chronicity of IH increased the protein levels of cyp1a1 protein (western blot). Daily administration (14 days) of AHR antagonist, CH-223191 (5 mg.kg-1.day-1, gavage), simultaneously to CIH prevented the increase in systolic blood pressure (SBP) by 53 ± 12% and in diastolic blood pressure (DBP) by 44 ± 16%. Moreover, this AhR antagonist administration upon already established HTN reversed the increase in SBP by 52 ± 12%. Despite the antihypertensive effect seen in the rats’ active phase, in the inactive period, CH22319 did not revert the non-dipping blood pressure profile associated to CIH.

Conclusions:

CIH caused an activation of AHR signaling particularly in the kidney and its pharmacological blockade had a significant impact reverting already established HTN. This first evidence inspires innovative research opportunities for the understanding and treatment of this particular type of HTN.
PREVALENCE AND PREDICTORS OF ADVERSE DRUG REACTIONS IN OLDER HYPERTENSIVE ADULTS
Authors: Turrin Giada , Coscarelli Antonio , D’andria Maria Flora , Tortu Virginia , Giuliani Evelina , Ungar Andrea , Rivasi Giulia
Published: April 2021

Objective:

Polipharmacy is common in older people, thus increasing the risk of adverse drufg reactrions. This study aimed to analyse prevalence and predictors of the most relevant adverse drug reactions in older hypertensive adults.

Design and method:

We retrospectively analysed data on antihypertensive- and statin-related adverse drug reactions in adults aged 65 or older evaluated at the Hypertension Clinic of Careggi Hospital, Florance, Italy, between January 2018 and December 2019. Predictors were investigated using multivariate logistic regression.

Results:

Of 262 participants (mean age 75.9 years, 55.3% female), the 19% of the patients taking ACE-inhibitors reported cough while 33.6% of the patients taking calcium channel blockers (CCB) reported peripheral edema, occuring more frequently of amlodipine. The prevalence of statin-related myalgia was 23.5%. At multivariate analysis SNRI antidepressants and gastroesophageal reflux disease (GERD) were predictive of ACE-inibitors induced cough (OR 16.220, 95% CI 1.243 – 211.621; OR 4.207, 95% CI 1.249 – 4.171, respectively) and angiotensin-receptor antagonists were associated with an increased risk of peripheral edema on CCB (OR 2.500, 95% CI 1.095 - 5.710). GERD was predictive for statin-induced myalgia (OR 6.737, 95% CI 1.530 - 29.662).

Conclusions:

ACE inhibitor-induced cough, CCB-related peripheral edema and statin-induced myalgia are common in older hypertensive adults. SNRI antidepressants and GERD are independently associated with ACE inhibitor-induced cough, while angiotensin-receptor antagonists are predictive of CCB-related peripheral edema. GERD is also associated with statin myalgia.
HUMAN AMNION EPITHELIAL CELLS REDUCE BLOOD PRESSURE AND PREVENT AORTIC INFLAMMATION AND COLLAGEN EXPRESSION DURING EXPERIMENTAL HYPERTENSION
Authors: Dinh Quynh Nhu , De Silva Cecilia , Diep Henry , Zhang Shenpeng R , Arce Liz J Barreto , Lim Rebecca , Drummond Grant R , Sobey Christopher G , Silva T. Michael De
Published: April 2021

Objective:

Vascular inflammation and fibrosis are hallmarks of hypertension and contribute to the development of cardiovascular disease. Current treatments for hypertension may reduce blood pressure but do not target the associated pathological changes and end-organ damage. Cell therapy has great therapeutic potential for many conditions as, unlike single pharmacological agents, cells can deliver multiple mediators which could more effectively target complex disease mechanisms. Human amnion epithelial cells (hAECs) have many properties (eg. anti-inflammatory, anti-fibrotic, regenerative and immunologically inert) that make them attractive candidates for a cell-based therapy for vascular pathology. This study aimed to test the potential of hAECs to treat vascular pathology in angiotensin II-induced hypertension.

Design and method:

Male C57Bl6 mice (8–12 weeks) were administered vehicle (saline; n = 35) or angiotensin II (0.7 mg/kg/d, n = 37) for 14 d via a subcutaneous osmotic minipump. After minipump implantation, a subset of mice were injected with 10^6 of hAECs intravenously. Systolic blood pressure was measured using tail-cuff; inflammation was assessed using flow cytometry and markers of fibrosis using quantitative PCR.

Results:

Angiotensin II infusion increased systolic blood pressure and promoted accumulation of aortic leukocytes, specifically macrophages and monocytes, which were elevated by ∼3-fold compared to vehicle-infused mice (n = 9–11, P < 0.05). Angiotensin II also increased aortic mRNA expression of collagen type 1 alpha 1 (Col1a1) by ∼4-fold and collagen type 5 alpha 1 (Col5a1) by ∼7-fold compared to vehicle (n = 6–8, P < 0.05). Co-administration of hAECs limited the development of hypertension by angiotensin II (185 ± 5 mmHg vs 165 ± 4 mmHg; n = 9–11, P < 0.05), as well as the aortic infiltration of macrophages and monocytes (n = 9–11, P < 0.05) and expression of Col1a1 and Col5a1 (n = 6–8, P < 0.05).

Conclusions:

Intravenous administration of hAECs blunted angiotensin II-induced hypertension, aortic inflammation and collagen expression in male mice. This study suggests that hAECs or their cellular products could be explored as treatments for vascular pathology during hypertension.
LOSS OF ADD1 METHYLATION ADDS ON BLOOD PRESSURE IN YOUNG ADULTS
Authors: Omar Wan Fatein Nabei Wan , Talib Norlelawati A. , Rahman Jamalludin Ab. , Shah Azarisman Shah Mohd , Abdullah Aszrin
Published: April 2021

Objective:

To investigate the association between alpha-Adducin (ADD1) methylation and blood pressure in young adults with essential hypertension.

Design and method:

A total of 160 subjects (80 normotensive and 80 incident hypertensive) aged between 18 to 45 years from Kuantan, Pahang were included in a cross-sectional study by purposive sampling. They were assessed for ADD1 methylation in peripheral blood using MethyLight assay. Anthropometric measurements and biochemical parameters were also examined.

Results:

ADD1 methylation was inversely correlated with systolic (p = 0.006, r = –0.240), diastolic (p = 0.001, r = –0.281) and mean arterial pressures (p = 0.002, r = –0.270). Hypertensive subjects had significantly higher ADD1 methylation than normotensive control (p = 0.005). After adjusting for other relevant covariates (age, body mass index, HbA1c, high-sensitivity C-reactive protein and low density lipoprotein cholesterol), ADD1 methylation remained a significant predictor for hypertension in young adults (p = 0.020)

Conclusions:

ADD1 methylation is a significant predictor of hypertension in young adults. ADD1 methylation could serve as a future preventive and therapeutic target for hypertension and related cardiovascular disease.
THE ROLE OF GUT METABOLITE-SENSING RECEPTORS GPR41 AND GPR43 IN CARDIOVASCULAR DISEASE
Authors: Muralitharan Rikeish R. , Nakai Michael , Paterson Madeleine , Jama Hamdi , Mackay Charles R. , Marques Francine Z.
Published: April 2021

Objective:

Fibre intake is associated with lower incidence of hypertension and cardiovascular mortality. Prebiotic fibre, such as resistant starches and soluble fibre, are fermented by commensal gut microbiota to short-chain fatty acids (SCFAs), which have a protective role in cardiovascular disease. We, and now others, have shown that supplementation of SCFA such as acetate, propionate and butyrate can reduce blood pressure (BP) and their complications. The main receptors for SCFAs, the G-coupled protein receptors GPR41 and GPR43, have redundant functions, but their contribution to cardiovascular health and disease is uncertain. Therefore, we aimed to characterize their contribution to the cardiovascular phenotype using a unique mouse model where both receptors are absent, the GPR41/43 knockout (KO)

Design and method:

We studied female (n = 12) and male (n = 15) double GPPR41/43 KO mice compared to wild-type (WT) C57BL/6 mice (n = 4–8) at 10 weeks of age. We performed BP measurements using tail cuff, sodium and water loading, real-time PCR, flow-cytometry of immune cells, and histology of the heart, kidney and gut

Results:

GPR41/43 KO male and female mice did not have significant difference in BP compared to WT mice (P = 0.387–0.676), but female GPR41/43 KO had significantly smaller kidneys (adjusted to tibia length) compared to WT female (P = 0.006). Upon saline challenge, both male and female GPR41/43 KO mice excreted more urine (P = 0.01 male, P = 0.116 female), but not sodium (P = 0.461 male, P = 0.141 female), compared to WT mice over a 5 hour period. GPR41/43 KO had lower levels of pro-renin receptor (Atp6ap2) mRNA (P = 0.012 male, P = 0.057 female) but higher levels of renal collagen genes mRNA (Col3a1 P = 0.055 male, Col1a1 P = 0.023 female), indicative of fibrosis.

Conclusions:

GPR41/43 KO mice expressed lower pro-renin receptor mRNA but higher levels of fibrosis markers. GPR41/43 KO mice excreted more urine than WT mice and did not have higher BP. Moreover, female GPR41/43 KO mice had significantly smaller kidneys, proposing a role for these receptors in renal development. Together, these findings suggest that the gut metabolite-sensing receptors GPR41/43 are likely to contribute to cardiovascular regulation via a role in water absorption and excretion, as well as in fibrosis
MIR-338-3P DOWN-REGULATION IN SMALL ARTERIES OF HYPERTENSIVE PATIENTS WITH CHRONIC KIDNEY DISEASE MAY ACT VIA UP-REGULATION OF ALKALINE CERAMIDASE 2 AND GLUTATHIONE PEROXIDASE 3
Authors: Paradis Pierre , Mahjoub Nada , Huo Ku-Geng , Berillo Olga , Richer Chantal , Fraulob-Aquino Julio C. , Briet Marie , Boutouyrie Pierre , Lipman Mark L. , Sinnett Daniel , Schiffrin Ernesto L
Published: April 2021

Objective:

Hypertension (HTN) is associated with vascular damage characterized by vascular remodeling and stiffening and endothelial dysfunction, which is a cause of end-organ damage such as chronic kidney disease (CKD). microRNAs are small non-coding RNA that regulate gene expression by binding to their target messenger RNAs (mRNAs), leading to mRNA degradation or translational repression. Their participation in mechanisms leading to vascular injury remains unclear. We aimed to identify differentially expressed (DE) microRNAs in small arteries of human subjects with HTN associated or not with CKD to gain insight into pathophysiological molecular mechanisms in these conditions.

Design and method:

Normotensive subjects and patients with HTN associated or not with CKD grades 3-4 were studied (n = 15-16). Blood pressure was determined by automated office measurement (AOBP). Small arteries were isolated from subcutaneous gluteal biopsies and RNA extracted for small and total RNA sequencing using Illumina HiSeq-2500. Differentially expressed (DE) genes were identified with a P < 0.05. The selected DE miRNAs were confirmed by reverse transcription-quantitative PCR (RT-qPCR). Putative microRNA targets were validated using gain- and loss-of-function in human aortic vascular cells by RT-qPCR and luciferase reporter assay.

Results:

Small RNA sequencing identified DE microRNAs uniquely associated with HTN (3 up and 6 down), CKD (42 up and 39 down) or both groups (2 up). One of 14 tested DE microRNAs was validated. RT-qPCR showed that miR-338-3p was decreased by 59% in CKD (P < 0.05). miR-338-3p and three of its predicted targets were highly expressed in human aortic endothelial cells (HAECs). Two of them, alkaline ceramidase 2 (ACER2) and glutathione peroxidase 3 (GPX3), were up-regulated by 48% and 90% in human aortic endothelial cells (HAECs) transfected with anti-miR-338-3p, respectively (P < 0.05). miR-338-3p mimic co-transfection in HAECs decreased respectively by 13% and 24% luciferase activity of reporter vectors containing the conserved wild-type but not mutated ACER2 or GPX3 3’ untranslated transcribed region miR-338-3p-5p binding sites (P < 0.05).

Conclusions:

miR-338-3p down-regulation in small arteries may act via mRNA up-regulation of alkaline ceramidase 2 and glutathione peroxidase 3 to play a role in vascular injury in hypertensive patients with chronic kidney disease.