bluuebunny/crossref_metadata_2025_split huggingface dataset:
SOCIOECONOMIC, DEMOGRAPHICS AND HEALTH CHARACTERISTICS OF ADULTS AND ELDERLY WITH SELF-REPORTED HYPERTENSION, UNDER TREATMENT OF ANTIHYPERTENSIVE THERAPY: A POPULATION BASED STUDY
Authors: Da Silva Brunna Raphaelly Amaral , Costa Karen Sarmento 
Published: April 2021

Objective:
To describe the socioeconomic, demographics and health characteristics of adults and elderly people who declared a diagnosis of hypertension, with a medical indication to treat that and was in use of antihypertensive drugs at the time of the interview.

Design and method:
Secondary data analysis from the National Survey on Access Use and Promotion of Rational Use of Medicines (PNAUM 2014), the nationwide cross-sectional population-based study, focused on the use of medicines in Brazil with a total of 41,433 interviews. The sample of this study consists of people who self-reported diagnosis of high blood pressure, medical indication to antihypertensive therapy and was in use of those medicines at the time of the interview. The Statistical Analysis System (SAS) version 9.4 was used.

Results:
The sample included 8,177 people with 20 years or more who reported a diagnosis of hypertension, medical indication for treatment with antihypertensive drugs, and were using them at the time of the interview. The use of antihypertensive drugs was distributed in a higher percentage among females, representing 64.4% of the sample, increased simultaneously with increasing age, ranging from 7.9% among individuals aged 20–39 years, to 50.4% among the elderly. Among the Brazilian regions, the use ranged from 4.4% in the North to 53.3% in the Southeast. Considering race/skin color the use of antihypertensives was 48.6% in Whites and 50.3% in Blacks. Individuals who reported being Indigenous and Yellow (Other), represented only 1.2%. People who claimed to have between 1 and 8 years of study and those in economic class C had higher percentages: 43.1% and 55.4% respectively. Describing variables of health conditions, 42% of respondents were overweight, 63.1% were non-smokers and 83% reported never consuming alcohol. Half of the sample reported having two or more chronic disease in addition to hypertension. Furthermore, 27.7% of respondents said they had hypercholesterolemia, 22.7% diabetes and 17.1% another chronic disease.

Conclusions:
The use of antihypertensive drugs occur mostly in Brazil among females, elderly, with 1 to 8 year of study, economic class level C, overweight, with two or more chronic disease in addition to hypertension.
THE IMPACT OF HYPERTENSION STATUS ON SURVIVAL IN THE RUSSIAN FEDERATION
Authors: Vladimir Kutsenko , Balanova Yulia , Imaeva Asiia , Kapustina Anna , Muromtseva Galina , Evstifeeva Svetlana , Karamnova Natalya , Maksimov Sergey , Yarovaya Elena , Shalnova Svetlana 
Published: April 2021

Objective:
To evaluate associations between hypertension and mortality among the Russian population.

Design and method:
A cross-sectional study Epidemiology of cardiovascular diseases in the RF (ESSE) was carried out in 14 regions of the Russian Federation (2012–13), response rate>80%. The prospective cohort included randomly selected males (N = 7243) and females (N = 11061) aged 25–64 (11 regions). Standard epidemiology methods and criteria were used. Arterial hypertension (AH) is defined as measured blood pressure (BP) of 140/90 mm Hg or greater and/or treatment with antihypertensive medications. Participants were divided into the four groups by BP levels and hypertension treatment: without hypertension (No AH), treated hypertensives who control their BP level (Controlling), hypertensives never treated (Untreated), and treated but not achieved target BP level (Not controlling). Endpoints were collected once every two years. The mortality follow-up period was 7 years, 397 deaths were observed.
Statistical data was processed using R 3.6.1. We used Kaplan-Meier estimator and log-rank test to investigate the relationship between risk groups and survival. We assessed the same relationship using the age-adjusted Cox proportional hazards model. P < 0.05 was considered as significant.

Results:
During the follow-up period, there were 83 deaths from coronary heart disease, 39 deaths – cerebrovascular accident, 20 deaths – other CVDs, 255 deaths – non-CVD. The impact of hypertension on survival was found among males and among females (p < 0.0001 for both) (fig. 1 A, B). The most significant total mortality risk was noted in the «Not controlling» group (males OR: 1.83, females OR: 1.59) (fig. 1 C, D). Similar results were obtained for CVD mortality (males OR: 2.72, females OR: 3.23, p < 0.005 for both). The survival in groups «Controlling» and «Untreated» did not differ significantly. However, «Controlling» participants were older than «Untreated» participants and had a larger waist size, greater prevalence of hyperlipidemia, and diabetes mellitus.

Conclusions:
The presence of hypertension significantly increases the risk of death. Treated but BP uncontrolled hypertensive subjects had the highest mortality risk. The absence of differences between «Controlling» and «Untreated» participants is due to differences in age and comorbidities.
LONG-TERM EFFECT OF ANTIHYPERTENSIVE AGENTS ON THE NEURAL BAROREFLEX SENSITIVITY-A SUBSTUDY OF THE PARIS PROSPECTIVE STUDY III
Authors: Fortier Catherine , Bruno Rosa Maria , Perier Marie-Cécile , Khettab Hakim , Guibout Catherine , Danchin Nicolas , Jouven Xavier , Empana Jean-Philippe , Boutouyrie Pierre 
Published: April 2021

Objective:
The baroreflex is a crucial mechanism regulating moment-to-moment blood pressure (BP) to ensure appropriate flow and pressure to the brain and other organs. All antihypertensive treatments, because of their BP lowering effect, interact with the autonomic nervous system by stimulating the sympathetic response. In addition, specific drugs may further interact with the BRS because of their specific mode of action. Whether antihypertensive agents have remnant effect is still unknown.

Design and method:
In the Paris Prospective Study III, spontaneous baroreflex, carotid stiffness and pharmacological drugs intake were available in 7967 adults (mean age of 60 ± 6 years, 62% men). The neural component of the baroreflex sensitivity (nBRS) was obtained with a cross-spectral analysis of variations in carotid distention rate and R-R intervals. Individuals with a BP lowering medication (BP-treated) were paired to non-BP treated individuals (controls) with similar cardiovascular comorbidities using a propensity score matching procedure (n = 1182 pairs).

Results:
Sympathetic activity was higher in the BP-treated group compared to their matched-controls, as shown by the increased spectral power of distention rate in the low frequency band (log LF distrate: 4.106 ± 0.530 vs 4.055 ± 0.514, p = 0.018). Amongst pharmacological classes of BP lowering agents, only agents acting on the angiotensin system (ACEi-ARB) were associated with nBRS. Compared to their matched controls (n = 331 pairs), ACEi-ARB users had lower nBRS (2.79 ± 0.66 (ln) vs. 2.90 ± 0.62 (ln), p = 0.03). After adjustment for carotid stiffness (stdbeta = 0.25, p < 0.001) and systolic pressure (stdbeta = -0.20, p < 0.001), ACEi-ARB remained significantly associated with nBRS (stdbeta = -0.09, p = 0.025).

Conclusions:
In this community-based population study, antihypertensive treatments induced activation of the autonomic nervous system independently of cardiovascular comorbidities. Taken as a whole, BP treatments did not have any effect on the neural component of the baroreflex loop, with the exception of ACEi-ARB which were negatively associated with nBRS. This effect was independent of BP and stiffness, which may suggest an inhibition of sympathetic activity by ACEi-ARB.
MICRORNA PROFILE IN HUMAN VASCULAR SMOOTH MUSCLE CELLS FROM HYPERTENSIVE SUBJECTS: FOCUS ON OXIDATIVE AND ENDOPLASMIC RETICULUM STRESS
Authors: Wang Yu , Camargo Livia L. , Beatie Wendy , Mcbride Martin , Montezano Augusto C. , Touyz Rhian M. 
Published: April 2021

Objective:
miRNAs are important to phenotypic control and function of vascular smooth muscle cells (VSMC). miRNA dysregulation is associated with vascular dysfunction, which involves oxidative and endoplasmic reticulum (ER) stress. We assessed VSMC miRNA profile in human hypertension focusing on oxidative and ER stress pathways.

Design and method:
VSMCs from small arteries from normotensive (NT) and hypertensive (HT) subjects were used. miRNA profiling of 758 miRNAs was performed using TaqMan advanced miRNA assay (TaqMan Low Density Array Human microRNA). Expression of vascular genes and proteins was detected by RT-PCR and immunoblotting respectively. Ingenuity Pathway Analysis (IPA) was used for miRNA target prediction (high predicted results).

Results:
miRNA array identified 25 miRNAs uniquely expressed in HT and 21 miRNAs uniquely expressed in NT (CT < 30). Of the 332 miRNAs present in both HT and NT, 60 miRNAs were significantly upregulated in HT (fold change >1.5), 136 miRNAs were significantly downregulated in HT (fold change >1.5). In HT, mRNA levels of Nox1 (1.71 fold) and protein levels of Nox4 (1.59 fold) and Nox5 (2.04 fold) were increased, p < 0.05. SOD2 (4.43 fold) and GPx1 (1.97 fold) protein expression were upregulated in HT, p < 0.05. PERK (1.57 fold) and elF2a (2.31 fold) protein levels were increased in HT, while ERO1A expression was decreased in HT (2.36 fold), p < 0.05. IPA was performed for the genes differentially expressed in HT compared to NT. After inversely pairing the miRNAs to the changes observed in gene and proteins expression, miR-505–5p (-2.13 fold), miR-324-5p (-1.51 fold), miR-185-5p (-1.742) and miR-491-5p (-1.667), which are predicted to target Nox5, were downregulated. miR-185-5p and miR-491-5p together with, miR-125a-3p (-2.04 fold) and miR-634 (unique in NT, CT = 27.36) were predicted to target GPx1. ER stress was also targeted by downregulated miRNAs in HT, such as miR-200b-3p (-28.57 fold), predicted to target elF2a.

Conclusions:
We identify a cluster of downregulated miRNAs in human hypertension that are linked to pathways that regulate oxidative and ER stress. These findings provide new molecular insights into processes underlying VSMC redox-sensitive dysfunction and may elucidate vascular miRNA signatures in human hypertension.
AFFERENT RENAL NERVE PATHWAYS IN RATS – RESPONSIVENESS TO HIGH SALT INTAKE
Authors: Rodionova Kristina , Ditting Tilmann , Fahrmeier Franziska , Ott Chirstian , Schmieder Roland , Schiffer Mario , Amann Kerstin , Veelken Roland 
Published: April 2021

Objective:
Afferent renal nerve pathways are likely involved in the development of salt sensitive hypertension. We recently reported that intrarenal NaCl elicited a long-lasting sympatho-depression via a neuro-humoral TRPV1 dependent and tachykinin mediated renal afferent nerve pathway. We now wanted to test the hypothesis that high sodium intake impairs this afferent sympatho-depressory mechanism.

Design and method:
Respective groups were put on tap water, 0.9 % saline for drinking or chow containing 8% NaCl. Cultured dorsal root ganglion neurons (DRG Th11-L2) of rats with renal afferents were investigated in current clamp mode to assess action potential generation during current injection. Rats were equipped with femoral catheters for blood pressure (BP) & heart rate (HR) assessment, drug application, a renal arterial catheter for intrarenal administration (IRA) of NaCl boli (10 % NaCl, 10 microl) or Capsaicin (CAP 10 ∗10-7 M, 10 microl) and a bipolar electrode for renal sympathetic nerve activity (RSNA) recordings; eventually an intravenous (iv) bolus of the NK1-receptor blocker RP67580 (10∗10-3 M, 15 microl) was administered. Results are mean ± SEM.

Results:
In neurons from rats on high salt diet, but not on 0.9 % saline or controls the relation of tonic highly active neurons to less active neurons shifted towards less active units. (62% tonic neurons in the control group and 63% tonic neurons in the saline group vs. 40%∗ tonic neurons in the high salt group, ∗ p < 0.05, z-test, mean +/-SEM). However, cultured renal neurons from rats on 0,9% saline or on high salt diet exhibited increased action potential production upon stimulation (controls 13,3+/11,03 APs/600ms vs. 0.9% saline 19,8+/-2,33∗ APs/600ms vs. high salt diet 22,2+/-4,54 APs/600ms, ∗ p < 0.05, t-test, mean+/-SEM). 10% NaCl boli IRA induced decreases of RSNA from baseline 4.1 ± 0.6 microV∗sec to 2.2 ± 0.8 microV∗sec impaired in rats on 8% NaCl.

Conclusions:
In rats on high salt diet highly active tonic neurons with renal afferents in vitro decreased at the expense of less active phasic neurons in spite of tonic neurons producing more action potentials upon stimulation. The sodium inducible long-lasting sympatho-depression via a neuro-humoral tachykinin mediated afferent renal nerve pathway was eventually impaired.
HIGH-DOSES OF LOSARTAN RATHER ACCELERATE THE SECRETION OF ADRENAL CATECHOLAMINES
Authors: Lim Dong Yoon , Cho Byung Ryul , Koh Young Youp 
Published: April 2021

Objective:
Previously, we have found that Losartan (5∼50 microM), an AT1 receptor blocker, dose-dependently inhibits secretion of catecholamines (CA) evoked by cholinergic and angiotensin II (Ang II) receptor stimulation from the perfused rat adrenal medulla. The aim of the present study was to examine the characteristic effects of high-dose losartan on the CA secretion from the isolated perfused rat adrenal gland, and also to establish its mechanism of action.

Design and method:
The adrenal gland was isolated and perfused with Krebs-bicarbonate. CA was measured directly by using the fluorospectrophotometer.

Results:
The perfusion of high-dose losartan (150 ∼ 600 microM) into an adrenal vein for 90 min resulted in great increases in CA secretions evoked by acetylcholine in a dose-dependent fashion. Also, losartan (300 microM) enhanced the CA release evoked by Ang II, high K+ and DMPP (a selective nicotinic receptor agonist), McN-A-343 (a selective muscarinic M1 receptor agonist). Also, in the presence of losartan (300 microM), the CA secretory responses to veratridine (a selective Na+ channel activator), Bay-K-8644 (a Ca2+ channel activator), and cyclopiazonic acid (a cytoplasmic Ca2+-ATPase inhibitor) were significantly potentiated, respectively. The facilitatory CA-releasing effect of Ach evoked by high-dose losartan (300 microM) was time-dependently depressed by pretreatment with nifedipine (Ca2+ channel blocker), while not by pretreatment with sodium nitroprusside (an NO donor). High-dose olmesartan (150 ∼ 600 microM), one of ARBs, also potentiated Ach-evoked CA release in time-dependent fashion. However, in the simultaneous presence of losartan (300 microM) and CGP42112 (an AT2 receptor agonist), the facilitatory responses of losartan on the CA secretion evoked by ACh were rather significantly reduced in comparison with that of losartan-treatment alone.

Conclusions:
Conclusively, these results demonstrate that high-dose losartan can potentiate the adrenomedullary CA secretion in a calcium-dependent fashion. It seems that this facilitatory effect of high-dose losartan may be mediated by activation of the Ca2+ influx through L-type Ca2+ channels into adrenomedullary cells without inhibition of NO synthesis, which seems to be relevant to AT2 receptor blockade. It also suggests that high-dose ARBs may be a risk factor in causing hypertensive response.
ALDOSTERONE CONTRIBUTES TO SYSTOLIC BLOOD PRESSURE ELEVATION DURING REST TIME IN MALE MICE INDUCIBLY OVEREXPRESSING HUMAN ENDOTHELIN-1 IN ENDOTHELIUM
Authors: Berillo Olga , Mahjoub Nada , Coelho Suellen C. , Offermanns Stefan , Paradis Pierre , Schiffrin Ernesto L. 
Published: April 2021

Objective:
The mechanisms of blood pressure (BP) regulation by endothelin (ET)-1 produced by endothelial cells (ECs) are complex and remain unclear. Transgenic mice with tamoxifen-inducible EC-restricted human ET-1 overexpression (ieET-1) exhibited BP elevation 3 months after induction. ET-1 has been shown to stimulate the release of aldosterone from adrenal cortex (AC). Whether aldosterone plays a role in EC ET-1 overexpression-induced BP elevation and vascular injury is still unknown.

Design and method:
Nine to 12-week-old male ieET-1 mice and control ieCre mice expressing a tamoxifen-inducible Cre recombinase under the control of EC-specific Tie2 promoter were treated with tamoxifen (1 mg/kg/day, SC) for 5 days and studied 3 months later. A set of mice was treated with eplerenone (100 mg/kg/day, PO), a mineralocorticoid receptor antagonist, or the ETA receptor blocker atrasentan (100 mg/kg/day) during the last 2 weeks of the study. BP was measured by telemetry and mesenteric artery function and remodeling by pressurized myography. Plasma aldosterone levels were measured by ELISA. The expression of genes involved in aldosterone biosynthesis was determined by reverse transcription-quantitative PCR in AC. CYP11B2 expression was determined in AC by immunofluorescence.

Results:
Plasma aldosterone levels were increased in ieET-1 vs. ieCre mice (1.21 ± 0.14 vs. 0.70 ± 0.09 ng/mL, P < 0.05), which was reversed by atrasentan. Cyp11b2 (aldosterone synthase), Hsd3b6 (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 6) and Cry1 (core-clock component cryptochrome 1) mRNA expression was decreased respectively by 50%, 39% and 31% in AC, and CYP11B2 protein expression was decreased by 51% in adrenal glomerulosa of ieET-1 vs. ieCre mice (P < 0.05). Two week eplerenone treatment reduced systolic BP by 10 mm Hg in ieET-1 mice during rest time (last 3 days, P < 0.05). Eplerenone abrogated the enhanced sensitivity of mesenteric arteries to contraction by norepinephrine in ieET-1 mice (P < 0.05), increased the sensitivity of endothelium-independent relaxation responses to sodium nitroprusside in ieET-1 mice (P < 0.05). Mesenteric artery media/lumen was reduced in eplerenone-treated ieET-1 vs. ieET-1 and ieCre mice (P < 0.05).

Conclusions:
These results demonstrate that aldosterone contributes to human EC ET-1 overexpression-induced BP elevation and vascular remodeling and norepinephrine sensitivity.
THE KALLIKREIN-KININ SYSTEM IS FALLING INTO PIECES: BRADYKININ FRAGMENTS ARE BIOLOGICAL ACTIVE PEPTIDES
Authors: Souza-Silva Igor Maciel , Paula Cristiane , Santos Anderson , Oliveira Vívian , Rocha Isabella , Antunes Maísa , Cordeiro Lídia , Teixeira Vanessa , Scalzo-Júnior Sérgio , Amaral Flávio , Resende Jarbas , Fontes Marco Antônio , Menezes Gustavo , Guatimosim Silvia , Santos Robson , Verano-Braga Thiago 
Published: April 2021

Objective:
Bradykinin [BK-(1–9)] is an endogenous peptide involved in many physiological and pathological processes, such as cardiovascular homeostasis and inflammation. The central dogma of the kallikrein-kinin system is that BK-(1–9) fragments are biologically inactive. In this work, we proposed to test whether these fragments were indeed inactive.

Design and method:
Nitric oxide (NO) was quantified in human, mouse and rat cells loaded with DAF-FM after stimulation with BK-(1–9), BK-(1–7), BK-(1–5) and BK-(1–3). We used adult male rat aortic ring preparation to test vascular reactivity mediated by BK-(1–9) fragments. Changes in blood pressure and heart rate was measured in conscious adult male rats by intraarterial catheter method.

Results:
BK-(1–9) induced NO production in all cell types tested by B2 receptor activation. BK-(1–7), BK-(1–5) and BK-(1–3) also induced NO production in all tested cell types but this response was independent of the activation of B1 receptor and/or B2 receptor. BK-(1–7), BK-(1–5) or BK-(1–3) induced only vasorelaxant effect and in a concentration-dependent fashion. Vasorelaxant effects for BK-(1–7), BK-(1–5) or BK-(1–3) were independent of the kinin receptors. BK-(1–9) induced in conscious adult male Wistar rats a dose-dependent hypotension while BK-(1–7), BK-(1–5) and BK-(1–3) induced a dose-independent hypotension. Importantly, these observations diverged from the BK-(1–9) results, highlighting that indeed the BK-(1–9) fragments do not seem to act via the classical kinin receptors.

Conclusions:
In conclusion, BK-(1–7), BK-(1–5) and BK-(1–3) are biologically active components of the kallikrein-kinin system. Importantly, observed pathophysiological outcomes of these peptides are independent of B1R and/or B2R activation.
ASSOCIATION OF AGT GENE M235T AND ACE GENE I/D POLYMORPHISMS WITH HYPERTENSION IN MONGOLIAN POPULATION
Authors: Unurjargal Tsolmon , Byambatsogt Bolortuul , Vanchin Byambasuren , Sodovsuren Naranchimeg , Davaakhuu Gantulga 
Published: April 2021

Objective:
In Mongolia, hypertension is major public health problem due to its high prevalence of stroke and mortality rate. The objective of this study was to analyse the relationship between AGT M235T gene variant and ACE I/D gene variant with hypertension in a sample of the Mongolian population of the Ulaanbaatar city.

Design and method:
Design and Method: A case-control study has been performed in 146 subjects including 96 hypertensives and 50 normo-tensive subjects, aged 18–60 years. Hypertension was defined as systolic BP =>130 mm Hg and/or diastolic BP=>80 mm Hg). After isolation DNA from peripheral blood, the following specific primers were used for polymerize chain reaction (PCR). PCR purification kit and QIAquick Gel extraction kit were used to establish nucleic acid sequence.

Results:
The mean age of the participants was 39.6 years and 54.7% were men. The M235T variant of AGT gene was identified in 97.9% of all participants (96.8% of hypertensive patients and 100% of normotensive subjects). According to the genotype results, the frequencies of the AGT TT, MT and MM genotypes were 57.3%, 39.6%, and 3.1% in cases and 64.0%, 36.0% and 0.0% in controls respectively.
The genotypic distribution of the M235T variant of the AGT gene did not differ in hypertensives and normotensives group (p > 0.328). In this study, we did not observe any significant differences in blood pressure levels with regard to ACE gene I/D polymorphism in both hypertensive and normotensive groups (40% vs 38%, p > 0.543).

Conclusions:
Conclusion: This is the first report on the frequency of AGT and ACE gene polymorphisms among Mongolian population. About 97.9% of Mongolians carry the M235T variant of the AGT gene that makes them more prone to hypertension when they eat too much sodium.