bluuebunny/crossref_metadata_2025_split huggingface dataset:
FIXED-DOSE COMBINATIONS IN THE TREATMENT OF HYPERTENSION IN THE RUSSIAN FEDERATION
Authors: Vladimir Kutsenko , Balanova Yulia , Shalnova Svetlana , Imaeva Asiia , Kapustina Anna , Muromtseva Galina , Evstifeeva Svetlana , Karamnova Natalya , Maksimov Sergey , Yarovaya Elena 
Published: April 2021

Objective:
To estimate the frequency of fixed-dose combinations (FDC) of antihypertensive medications (AHM) in the hypertension treatment in the population of the Russian Federation (RF).

Design and method:
A cross-sectional study ‘Epidemiology of Cardiovascular Diseases in the RF (ESSE-RF)’ was performed in 13 regions (2012–2013). Randomly selected males (N = 8304) and females (N = 13464) aged 25–64 were included (response rate>80%). Standard epidemiology methods and criteria were used. Hypertension defined as a measured blood pressure (BP) of 140/90 mm Hg or greater and/or treatment with AHM. The structure of FDC in AHM was investigated. AHM have been analyzed by the following classes: diuretics (D), betablockers (BB), calcium antagonists (CA), angiotensin converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARBs), and «other». In addition, FDC of AHM have been studied. Statistical data was processed using R 3.6.1 (R Foundation for Statistical Computing, Vienna, Austria).

Results:
Results The prevalence of hypertension and treatment in the RF was 45,7% and 51.8%. Among hypertensive patients who were receiving treatment, 65.6% were taking 1 AHM, 2 – 23.1%, 3 and more – 6.7%, whereas 4,6% were taking non-AHM. The most commonly taken medications were ACEi (58.4%), BB (34.9%), and D (32.4%)
The frequency of taking an FDC of AHM was 15.6%. Among those taking FDC the most frequently employed were D+ACEi (49.3%), D+ARBs (24.8%), and D+BB (17.2%) fig 1.

Conclusions:
Despite the importance of BP control in preventing cardiovascular and cerebrovascular events, only 1/3 of hypertensive patients in the RF have their BP under control. Prescription frequency of an FDC of AHM remains low – only every sixth patient with hypertension taking medications applied the FDC.
OUTCOMES OF PATIENTS WITH ST SEGMENT ELEVATION MYOCARDIAL INFARCTION AND LEFT VENTRICULAR HYPERTROPHY: 25-YEAR POPULATION-BASED STUDY
Authors: Ghrab Aiman , Chamtouri Ikram 
Published: April 2021

Objective:
Left ventricular hypertrophy is a common finding in hypertensive patients. The increase in myocardial masse is accompanied with an elevation of oxygen demand. The occlusion of a coronary artery in ST-segment elevation myocardial infarction (STEMI) leaves the myocardium without oxygen supply. This depletion is harmful to myocardial cells and its effect could be more important in left ventricular hypertrophy patients.

Aim:
To evaluate the effect of left ventricular hypertrophy on Stemi outcomes.

Design and method:
Patients with STEMI underwent an echocardiographic exam within two days from the event and left ventricular hypertrophy (LVH) was evaluated using the left ventricular mass calculated using echocardiography.
The primary endpoints were in-hospital and 1-year cardiovascular events. The secondary endpoints were left ventricular ejection fraction.

Results:
In total, 1605 patients were admitted for STEMI. There were 489 hypertensive patients. 28% had LVH.
There was no difference in risk-adjusted in-hospital mortality between patients with and without LVH (p = 0,149). Both groups showed the same risks of developing life threatening arrythmias (p = 0,287).
Left ventricular ejection fraction was evaluated in both groups. Patients with LVH did not have more risk of systolic dysfunction than the other group of patients (p = 0,098).

Conclusions:
Patients with left ventricular hypertrophy undergoing STEMI had similar outcomes compared to patients without LVH.
WHAT IS THE MAJOR FACTOR ON THE KIDNEY INJURY INDUCED BY HYPERTENSION OR HYPERHOMOCYSTEINEMIA
Authors: Xu Rui , Gao Ning 
Published: April 2021

Objective:
As we all know kidney injury could be induced by hypertension or hyperhomocysteinemia (HHcy). What is the major factor? HHcy plays a synergistic role with hypertension in vascular injury; however, the relationship between HHcy and hypertension in renal injury remains unclear. Here, we sought to evaluate the relationship between HHcy and hypertension in the context of renal injury and to elucidate the mechanism of action underlying this relationship.

Design and method:
Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats were randomized into WKY, WKY+HHcy, SHR, and SHR+HHcy groups. Blood pressure, plasma homocysteine, creatinine, serum malondialdehyde (MDA), serum superoxide dismutase (SOD), and urinary albumin creatinine ratio (UACR) were measured. mRNA and protein expression levels of NOX2, NOX4, and nephrin in the kidneys were also examined.

Results:
The WKY+HHcy group exhibited lower serum SOD levels, relative to the WKY group, along with higher levels of both serum MDA and UACR. Similar effects were observed in the SHR+HHcy group, relative to the SHR group. Moreover, compared with the levels in the WKY+HHcy group, mean SOD levels in the SHR+HHcy group were lower, while mean MDA and UACR levels were higher. Higher mRNA and protein expression levels of NOX2 and NOX4, along with lower mRNA and protein expression levels of nephrin, were observed in the kidneys of WKY+HHcy and SHR+HHcy rats, relative to SHR and WKY controls, respectively. Furthermore, the mRNA and protein levels of NOX2 and NOX4 were higher and the mRNA and protein levels of nephrin were lower in the SHR+HHcy group than in the WKY+HHcy group. In addition, compared with WKY+HHcy group, the UACR level of SHR group was higher.

Conclusions:
HHcy appears to synergistically increase hypertensive renal damage by enhancing oxidative stress. However, hypertension remains a major risk factor for renal impairment compared to HHcy.
RESVERATROL PROTECT AGAINST HOMOCYSTEINE-INDUCED RENAL DAMAGE THROUGH ANTIOXIDANT ACTION IN SPONTANEOUS HYPERTENSIVE RATS
Authors: Xu Rui , Hui Qingchen , Zhao Xuan 
Published: April 2021

Objective:
The aim of this study was to investigate the effect of resveratrol in renal damage and the underlying mechanism induced by Hhcy in SHRs.

Design and method:
Twenty-four SHRs were divided into control group, Hhcy group, Hhcy + resveratrol (Hhcy+Res) group. Hhcy groups were given intraperitoneal injection of homocysteine. In addition, the Hhcy + Res group was given resveratrol by gavage. The Systolic blood pressure (SBP), diastolic blood pressure (DBP), plasma Hcy, serum malondialdehyde (MDA), superoxide dismutase (SOD) and the urinary microalbumin (UACR) were measured. To quantify RNA and protein expression levels, the mRNA and the protein expression of nephrin and NADPH oxidase subunits NOX2 and NOX4 in the kidney were examined by quantitative Real-time PCR and western blot. Renal histological or pathological changes were observed under light and electron microscope.

Results:
There was no difference in blood pressure before and after Hcy or Res intervention among groups. The homocysteine levels in Hhcy and Res group were significantly higher than that in control group, which showed that the model was successfully built by intraperitoneal injection. The serum SOD level was significantly decreased in Hhcy group, while it was increased in Res group. On the contrary, the serum MDA and UACR levels of model group were significantly increased. after the intervention of resveratrol, the MDA and UACR levels were reduced. Furthermore, the expression levels of mRNA and the protein of NOX2 and NOX4 were elevated while those of the nephrin were reduced in Hhcy group. Resveratrol significantly reduced the expressions of NOX2 and NOX4, and increased the expression of nephrin in renal tissue of SHRs with Hhcy.

Conclusions:
These results suggested that resveratrol may improve renal damage in hypertensive rats with Hhcy by exerting oxidative stress beyond blood pressure.
DIFFERENT FORMS OF AFFERENT NERVE INPUT IN CARDIAC AND RENAL DISEASE IN RATS?
Authors: Rodionova Kristina , Ditting Tilmann , Pickny Lisa , Ott Christian , Schmieder Roland , Schiffer Mario , Amann Kerstin , Veelken Roland 
Published: April 2021

Objective:
Afferent nerve pathways form kidney and heart are said to control sympathetic renal nerve activity. In a renal disease model the responsiveness of afferent renal nerve units was shifted from units with highly active primary neurons (tonic response pattern) to units with neurons of very low activity upon stimulation (phasic response pattern). Afferent renal nerve activity was likely decreased. Likewise, afferent vagal nerve activity in congestive heart failure (CHF) had a lower frequency at saturation than controls. Hence we wanted to test the hypothesis that CHF the vagal afferent nerve pathway consists of a decreased number of highly active tonic sensory neurons in the nodose ganglion.

Design and method:
CHF was induced by coronary artery ligature, nephropathy by injections of an anti Thy1.1 antibody (OX7, 1.2 mg/kg). After a respective time (CHF 21 days, nephropathy 7 days after induction) nodose ganglion neurons with cardiac vagal afferents from CHF rats or neurons form dorsal root ganglia with renal afferents from rats with nephropathy were cultured. Current clamp was used to characterize neurons as tonic, i.e. sustained action potential (AP) firing or phasict, i.e. <5 APs upon current injection. More than 100 neurons were investigated.

Results:
In CHF rats, the number of neurons with a tonic response pattern did not differ from controls (64% vs. 70 %, ns). However, tonic cardiac neurons from CHF rats exhibited an increased production of action potentials compared (24.4+/-5.0 vs. 14.7+/-1.8 APs/10 s; p < 0.05; mean+/-SEM). In nephropathic rats, the number of neurons with a tonic response pattern decreased significantly (43% vs. 64 %, p < 0.05), but there was no difference in action potential production between groups.

Conclusions:
In congestive heart failure the number of afferent neurons with a tonic response pattern was not significantly altered. However, the action potential production of these neurons even significantly increased upon stimulation. Hence, in congestive heart failure vagal afferent neurons increase their sensitivity in the presence of impaired intracardiac receptors whereas in renal disease the responsiveness of the first part of the afferent pathway is impaired as a whole.
DIFFERENTIAL EXPRESSION OF VASCULAR DYSFUNCTION OF SMALLER DIAMETER ARTERIES IN A RODENT MODEL OF METABOLIC SYNDROME
Authors: Salman Ibrahim , Ameer Omar , Alwadi Aiman 
Published: April 2021

Objective:
Metabolic syndrome, driven by obesity and diabetes, is a major contributor to cardiovascular disease. While large arteries vascular dysfunction is a well-documented phenomenon of metabolic syndrome, vascular disease of smaller diameter arteries, which are key contributors to peripheral vascular resistance and blood pressure control, remains uncertain. Using in-vitro organ-bath preparation, this study, therefore, investigated functional responses of the superior mesenteric and right iliac arteries in a high fat diet (HFD)/streptozotocin-induced diabetes mellitus rat model.

Design and method:
Five-week-old male Wistar Albino rats (n = 24) were fed with either HFD (45 kcal% fat) or control diet (10 kcal% fat) for 10 weeks. At 10 weeks of age, 40 mg/kg streptozotocin and saline were injected intraperitoneally into the HFD and control groups, respectively.

Results:
Diabetic HFD rats displayed a time-dependent increase (p < 0.01) in water intake, urine output, fasting blood glucose and tailcuff systolic blood pressure compared to controls (154 ± 6 vs. 110 ± 4 mmHg). Both mesenteric and iliac vasoconstrictor responses (N/g) to norepinephrine (1E-9 – 3E-5 M), but not to the depolarizing signals of high potassium (5 – 120 mM), were greater (p < 0.01) in the HFD group relative to controls. Mesenteric, but not iliac, endothelium-dependent vasorelaxation to acetylcholine (1E-10 – 1E-5 M) was blunted (p < 0.05) in the HFD rats compared with controls. In contrast, mesenteric and iliac endothelium-independent vasorelaxation responses to sodium nitroprusside (1E-11 – 1E-6 M) remained comparable between groups.

Conclusions:
Vascular functional responses in smaller diameter arteries are differentially expressed in metabolic syndrome, demonstrating upregulated vasoconstriction to adrenergic stimuli and/or impaired endothelium-dependent relaxation. These vascular abnormalities align with those previously described in larger arteries and could therefore further promote the development of cardiovascular disease in metabolic syndrome.
CENTRAL INTEGRATION OF LEFT VERSUS RIGHT BARORECEPTOR AFFERENT INPUT IN FEMALE SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Salman Ibrahim , Ameer Omar , Mcmurray Sheridan , Sridhar Arun , Lewis Stephen , Hsieh Yee-Hsee 
Published: April 2021

Objective:
Neuromodulation of blood pressure using baroreflex activation therapy is an effective means to control hypertension in resistant hypertensive patients. In a genetic rat model of essential hypertension, the spontaneously hypertensive rats (SHRs); we were able to demonstrate in male rats that preferential central integration of left baroreceptor afferent input exists relative to that of the right afferents. It remains unknown whether laterality also influences baroreflex responses in female SHRs. Accordingly, the differences in cardiovascular responses triggered by stimulation of the left and right baroreceptor afferents, as assessed by direct electrical stimulation of the aortic depressor nerve (ADN), were studied in female SHRs.

Design and method:
Pentobarbital-anesthetized female SHRs (25–29 weeks, n = 6–8) were instrumented for left and right ADN stimulation (1–40 Hz, 0.2 ms, 0.4 mA for 20 s) and recording of mean arterial pressure (MAP), heart rate (HR) and mesenteric (MVR) and femoral (FVR) vascular resistance. Female rats were also matched for the diestrus phase of the estrus cycle.

Results:
Both left and right ADN stimulation resulted in frequency-dependent reductions (P < 0.001) in MAP, HR, MVR and FVR. Reflex reductions in MAP, HR, MVR and FVR were comparable for both left-sided and right-sided stimulation.

Conclusions:
Unlike males, female SHRs express no differential central modulation of baroreceptor afferent input as evidenced by the comparable left versus right baroreflex-mediated depressor responses. Similar depressor responses in the left versus right stimulation may have been contributed to by the lack of differences in baroreflex-driven changes in HR and vascular resistance. Clinically, targeting either the left or right aortic nerves may equally provide adequate reductions in blood pressure in female hypertensive subjects. Future studies should elucidate the mechanisms responsible for sex differences in the central processing of baroreflex between male and female SHRs.
EFFECTIVE AND SAFE COMBINATION OF ATORVASTATIN AND EZETIMIBE THERAPY IN PATIENTS WITH ISCHAEMIC HEART DISEASE
Authors: Gamage Nadun Danushka Pitiduwa , Samarasekara Tharanga , Kottage Menaka , Muthumudalige Emashi 
Published: April 2021

Objective:
Dyslipidaemia (DL) is a well-known risk factor for Cardiovascular disease(CVD). Literature suggests combined therapy of Atorvastatin and Ezetimibe (A&E) is beneficial than Atorvastatin therapy alone. Objective of the study is to determine the effective and safe dose combination of A&E in patients with Ischaemic heart disease (IHD) in patients attending to the cardiology clinic.

Design and method:
Four separate treatment regimens were administered in randomly assigned 4 groups of patients. Each group was given same dose of Ezetimibe (10 mg). Atorvastatin doses were given as 10 mg (G1), 20 mg (G2), 30 mg (G3), 40 mg (G4) etc. After baseline investigations, patients were followed up for 6 months and reevaluation was done. Non parametric tests were used for data analysis. Ethical clearance was obtained prior to the study.

Results:
Overall 110 patients were recruited. Mean age was 60.1 ± 9.4 years and female predominance (62.7%) was observed.
Significant reduction of total cholesterol (TC), low density lipoprotein (LDL) were observed in G2 (p = 0.009 and p = 0.003 respectively) and G4 (p = 0.006 and p = 0.001). However, no statistically significant change was observed in high density lipoprotein (HDL) and triglyceride (TG). No significant rise in serum creatinine (p = 0.08) and liver function tests were observed. And it is not found any statistically significant change of FBS before and after the treatment

Conclusions:
Combined therapy of Ezetimibe 10 mg with Atorvastatin 20 mg or 40 mg would be significantly reduce the TC and LDL in the patients with IHD. But it does not the improve HDL and TG levels. Use of Atorvastatin 10 mg and 30 mg did not show any significant improvement of entire lipid profile.
EFFECTS OF A GLUCAGON LIKE PEPTIDE-1 AGONIST AND RHO-KINASE INHIBITOR ON PULMONARY AND RIGHT VENTRICLE FUNCTION IN PULMONARY HYPERTENSIVE RATS WITH AND WITHOUT INSULIN RESISTANCE
Authors: Pearson James , Jin Huiling , Waddingham Mark , Sonobe Takashi , Maeda Hisashi , Ngo Jennifer , Ow Connie , Sukumaran Vijayakumar , Ogo Takeshi , Shirai Mikiyasu , Tsuchimochi Hirotsugu , Ueda Hatsue-Ishibash 
Published: April 2021

Objective:
Insulin resistance is now recognized as an important factor in the development of pulmonary hypertension (PH). Increased activation of RhoA/Rho-kinase (ROCK) inhibits the protective actions of endothelial nitric oxide (NO) synthase (eNOS) signaling in diabetes and PH. Glucagon like peptide-1 (GLP-1) agonists were shown to reverse these pathological changes. We investigated how liraglutide (GLP-1 agonist) and fasudil (ROCK inhibitor) treatments affect the progression of pulmonary and right ventricle (RV) dysfunction in PH rats with insulin resistance.

Design and method:
SU5416 (20 mg/kg) was administered to male Wistar and prediabetic Goto-Kakizaki (GK) rats followed by 3 weeks of chronic hypoxia (SuHx) or normoxia exposure. Osmotic pumps delivered a continuous infusion of liraglutide (1 mg/kg/d) or fasudil (100 mg/kg/d) for the final 3 weeks in some SuHx rats. Synchrotron microangiography of the left lung was performed in vivo.

Results:
During chronic hypoxia 30% mortality occurred due to RV failure associated with thrombosis in GK rats. Systolic RV pressure was 74 mm Hg and 128 mm Hg in GK and Wistar SuHx rats respectively. Prediabetes exacerbated pulmonary arteriole-artery rarefaction (two-fold occlusion increase) and pulmonary vasoconstriction, with acetylcholine (ACh)-mediated constriction at 3 weeks and loss of NO donor mediated dilation at 6 weeks SuHx. Wistar SuHx maintained ACh-mediated dilation in resistance vessels despite pronounced overall vasoconstriction of all branching orders. Neither strain differed in ROCK1/2 protein expression. Notably, liraglutide and fasudil improved pulmonary vasodilation, but only liraglutide halted vascular remodeling. Fasudil increased phosphorylation of eNOS at Ser1177 in the RV of GK SuHx. Liraglutide reduced RV systolic pressure and Fulton indices, while fasudil elevated RV pressure to 104 mm Hg in the GK SuHx.

Conclusions:
Reduced NO bioavailability contributes to exacerbated pulmonary arterial rarefaction and depressed RV contractility associated with prediabetes in SuHx rats. GLP-1 agonist treatment did not ameliorate endothelin-1/ROCK- mediated suppression of eNOS phosphorylation in the RV as observed with fasudil. While liraglutide intervention prevented pulmonary microvessel occlusion, inhibition of both ROCK1/2 isoforms with fasudil increased occlusion formation suggesting that ROCK1 might act to inhibit pulmonary microvessel muscularization.
COMPARISON OF INHIBITORY EFFECTS EVOKED BY OLMESARTAN AND ENALAPRIL ON CATECHOLAMINE SECRETION
Authors: Lim Dong Yoon , Koh Young Youp 
Published: April 2021

Objective:
The present study was designed to compare enalapril, an angiotensin converting enzyme inhibitor (ACEI) with olmesartan an angiotensin II receptor blocker (ARB) in the inhibitory effects on the secretion of catecholamines (CA) from the perfused model of the rat adrenal gland.

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

Results:
Both enalapril (50 microM) and olmesartan (50 microM) during perfusion into an adrenal vein for 90 min inhibited the CA secretory responses evoked by ACh (5.32 microM), DMPP (a selective neuronal nicotinic Nn receptor agonist, 100 microM), high K+ (a direct membrane-depolarizer, 56 mM), and McN-A-343 (a selective muscarinic M1 receptor agonist, 100 microM) in a time-dependent manner. Also, in the presence of enalapril or olmesartan, the secretory responses of CA evoked by veratridine (an activator of voltage-dependent Na+ channels, 100 microM), Bay-K-8644 (a L-type dihydropyridine Ca2+ channel activator, 10 microM), and cyclopiazonic acid (a cytoplasmic Ca2+-ATPase inhibitor, 10 microM) were significantly reduced. Based on the same concentration (50 microM) of enalapril and olmesartan, for the CA release evoked by Ach, high K+, DMPP, McN-A-343, angiotensin II, veratridine, Bay-K-8644 and cyclopiazonic acid, the following rank order of inhibitory potency was obtained: olmesartan> enalapril. In the simultaneous presence of enalapril and olmesartan, Ach-evoked CA secretory responses were more strongly inhibited in comparison with that of enalapril- or olmesartan-treated alone.

Conclusions:
Collectively, these results demonstrate that both enalapril and olmesartan inhibit the CA secretory responses evoked by activation of both cholinergic and angiotensin II receptors stimulation as well as by direct membrane depolarization in the perfused model of the isolated rat adrenal medulla. When these two drugs were used in combination, their effects were enhanced, which may also be of clinical benefit. Based on concentration used in this study, it seems that the inhibitory effect of olmesartan on the CA secretion is more potent than that of enalapril.