Pathophysiology Of Arterial Hypertension Research Articles

Controversies in the pathophysiology of arterial hypertension.

Introduction: Purinergic receptors actively participate in the renal alterations in high blood pressure. The elevation of ATP in the renal interstitium activates purinergic receptors, constituting a fundamental pathway in the generation and persistence of arterial hypertension. Objective of the review: This article is a narrative review that aims to show the importance of new concepts in the pathophysiology of arterial hypertension. Essential points of the review: Purinergic receptors are ATP receptors; the more significant the ATP, the greater the purinergic receptors. Elevated ATP concentrations alter fundamental mechanisms related to blood pressure control, such as the pressure natriuresis mechanism and renal sodium excretion, the regulation of glomerular filtration, and the tubuloglomerular feedback mechanism. The alteration of these mechanisms decreases urinary sodium excretion. Whether influenced by genetic alterations or induced by vasoconstrictor peptides, a decrease in renal function and tubulointerstitial injury occur before the glomerulus is injured. The interaction between angiotensin II and purinergic receptors favors the progression of kidney damage. Conclusion: Kidney damage in high blood pressure is critical, so efforts should be made to control hypertension to prevent the progression of kidney damage that leads to kidney failure. To obtain better blood pressure control, developing purinergic receptor antagonists for clinical use is possible.

Association between skin lymphangiogenesis parameters and arterial hypertension status in patients: An observational study.

Recent studies have indicated that the skin lymphatic system and interstitium may play a role in the pathophysiology of arterial hypertension (AH). We aimed to determine whether the set of pathway parameters described previously in rodents would allow for the distinction between hypertensive and normotensive patients. Molecular and histopathological parameters from the skin and blood of patients with AH (AH group, n = 53), resistant AH (RAH group, n = 32) and control (C group, n = 45) were used, and a statistical multivariate bootstrap methodology combining partial least squares-discriminant analysis (PLS-DA) and selectivity ratio (SR) were applied. The C vs RAH model presented the best prediction performance (AUC test = 0.90) and had a sensitivity and specificity of 73.68% and 83.33%, respectively. However, the parameters selected for the C vs AH group model were the most important for the pathway described in the rodent model, i.e., greater density of the skin lymphatic vessels (D2-40 expression) and greater number of macrophages (CD68 expression), higher expression of the messenger ribonucleic acid (mRNA) of nuclear factor of activated T cells 5 (NFAT5), vascular endothelial growth factor C (VEGFC) and podoplanin (PDPN) in the skin, greater concentration of hyaluronic acid (HA) in the skin, and lower serum concentration of VEGF-C. Our study suggests that the NFAT5/VEGF-C/lymphangiogenesis pathway, previously described in rodent studies, may also be present in human HA. Further experiments are needed to confirm our findings.

Concurrent exercise training potentiates the effects of angiotensin-converting enzyme inhibitor on regulatory systems of blood pressure control in ovariectomized hypertensive rats.

Enalapril has shown satisfactory potential in controlling increased and sustained blood pressure (BP). However, multiple dysregulated mechanisms that interact with each other and are involved in the pathophysiology of arterial hypertension may not be affected, contributing to the remaining cardiovascular risk. Using an exercise training protocol, we investigated whether adding both approaches to arterial hypertension management could promote higher modulation of regulatory mechanisms of BP in postmenopausal rats. Spontaneously hypertensive rats were allocated into sedentary (S) and ovariectomized groups: sedentary (OS), sedentary treated with enalapril maleate (OSE) and trained treated with enalapril maleate (OTE). Both the pharmacological and exercise training protocols lasted for 8 weeks. The BP was directly recorded. Inflammation and oxidative stress were evaluated in the cardiac tissue. Although BP reduction was similar between OSE and OTE, trained group showed lower vasopressor systems outflow after sympathetic ganglion blocking by hexamethonium (mean BP) (OTE: -53.7 ± 9.86 vs. OS: -75.7 ± 19.2 mmHg). Bradycardic and tachycardic response were increased in OTE group (-1.4 ± 0.4 and -2.6 ± 0.4 vs. OS: -0.6 ± 0.3 and -1.3 ± 0.4 bpm/mmHg, respectively), as well as BP variability. In addition, the combination of approaches induced an increase in interleukin 10, antioxidant defense (catalase and glutathione peroxidase) and nitrite levels compared with the OS group. Despite similar BP, the inclusion of exercise training in antihypertensive drug treatment exacerbates the positive adaptations induced by enalapril alone on autonomic, inflammatory and oxidative stress profiles, probably affecting end-organ damage and remaining risk.

Sodium accumulation in the skin is associated with higher density of skin lymphatic vessels in patients with arterial hypertension

PurposeRecent studies, conducted mainly on the rodent model, have demonstrated that regulatory pathway in the skin provided by glycosaminoglycans, nuclear factor of activated T cells 5 (NFAT5), vascular endothelial growth factor C (VEGF-C) and process of lymphangiogenesis may play an important role in extrarenal regulation of sodium (Na+) balance, body water volume, and blood pressure. We aimed to investigate the concentrations and relations among the main factors of this pathway in human skin to confirm that this regulatory axis also exists in humans. Patients and methodsSkin specimens from patients diagnosed with arterial hypertension and from control group were histologically and molecularly examined. ResultsThe primary hypertensive and control groups did not differ in Na+ ​concentrations in the skin. However, the patients with hypertension and higher skin Na+ concentration had significantly greater density of skin lymphatic vessels. Higher skin Na+concentration was associated with higher skin water content. In turn, skin water content correlated with factors associated with lymphangiogenesis, i.e. NFAT5, VEGF-C, and podoplanin (PDPN) mRNA expression in the skin. The strong mutual pairwise correlations of the expressions of NFAT5, VEGF-C, vascular endothelial growth factor D (VEGF-D) and PDPN mRNA were noted in the skin in all of the studied groups. ConclusionsOur study confirms that skin interstitium and the lymphatic system may be important players in the pathophysiology of arterial hypertension in humans. Based on the results of our study and existing literature in this field, we propose the hypothetical model which might explain the phenomenon of salt-sensitivity.

INCREASED RISK OF NEW ONSET OF ARTERIAL HYPERTENSION IN PATIENTS WITH MULTIPLE MYELOMA TREATED WITH CARLFIZOMIB

Objective: Several new drugs are used nowadays to treat multiple myeloma (MM). Some drugs are loaded with an increased risk of developing cardiovascular diseases. Carfilzomib (K), a proteasome inhibitor, is well recognized to cause cardiovascular side effects. Also, arterial hypertension is a main factor leading to LV dysfunction. Purpose is to evaluate if patients who underwent the carfilzomib treatment may present an increased incidence of arterial hypertension. Design and method: We evaluated 34 patients (group K, 20M, 14F, aged 65.87±5.98) treated with carfilzomib: 25 patients were given 56 mg/m2 (group 1, 14M, 9F, aged 67.30±5.98) while 9 27 mg/m2 (group 2, 6M, 3F, aged 63.00±5.39). As controls, we recruited 34 patients (16M, 18F, aged 69.80±9.13) who underwent in the same period the MM treatment without carfilzomib. Hypertension was identified as new onset of disease or worsening of disease (need double the dose used, add a new drug, or no pressure control in at least 3 drugs treatments). Results: At baseline, the controls presented an increased arterial hypertension rate (76.47% vs group K 47.06%, p = 0.07). There was no difference in any other CVD risk factor. There was no difference in LV mass, volumes and ejection fraction. The group K experienced an increased incidence of arterial hypertension compared to controls (controls 0% vs group K 41.17 %, p = 0.001). This result was not related to the drug dose. Finally, there was no difference in mortality between the two groups also by analysing the CV death. Conclusions: Carfilzomib is a potent and effective drug in MM. Its cardiovascular toxicity relates to a vascular and endothelial damage leading to a new onset of arterial hypertension. This observation may be useful in preventing evolution of the CV dysfunction in survivors and long survivors MM patients. Also, it may be important for studies of vascular damage in arterial hypertension pathophysiology.

Angiotensin-converting enzyme gene (ACE) polymorphisms are associated with dysregulation of biochemical parameters in hypertensive patients.

The genetic component, including genes and their variants, plays a significant role in the pathophysiology of arterial hypertension (AH). Thus, clinical, epidemiological and genetic studies have been carried out to improve the understanding of disease mechanisms, improve diagnostic quality and contribute to prevention. To determine the association of risk factors, biochemical parameters and different ACE gene polymorphisms with AH. The case-control study was carried out in the population of Ouro Preto, Brazil. The subjects answered a questionnaire containing clinical and sociodemographic data. The ACE gene polymorphisms rs4291, rs4363 and rs4335 were evaluated by real time-polymerase chain reaction (real-time PCR) in 310 people (155 hypertensive and 155 normotensive patients), in addition to biochemical parameters. A multivariate logistic regression model was used to identify factors associated with AH. Analysis of continuous variables was performed using the Kruskal-Wallis test to assess significance between groups and Dunn's post-test for multiple comparisons. The results showed that AH was associated with age, education, smoking, obesity and high levels of triglycerides, sodium, glucose and uric acid. Regarding the biochemical parameters, in hypertensive patients, the rs4363 and rs4335 polymorphisms were associated with high levels of triglycerides, urea and glucose; the rs4291 polymorphism was associated with elevated urea and glucose levels. No association was detected between SNPs and HA. AH was associated with socioeconomic status, lifestyle habits and biochemical parameters. ACE polymorphisms may have influenced the levels of triglycerides, urea and glucose in hypertensive patients.

Pathophysiology of Cardiovascular Diseases: New Insights into Molecular Mechanisms of Atherosclerosis, Arterial Hypertension, and Coronary Artery Disease.

Cardiovascular diseases (CVDs) are disorders associated with the heart and circulatory system. Atherosclerosis is its major underlying cause. CVDs are chronic and can remain hidden for a long time. Moreover, CVDs are the leading cause of global morbidity and mortality, thus creating a major public health concern. This review summarizes the available information on the pathophysiological implications of CVDs, focusing on coronary artery disease along with atherosclerosis as its major cause and arterial hypertension. We discuss the endothelium dysfunction, inflammatory factors, and oxidation associated with atherosclerosis. Mechanisms such as dysfunction of the endothelium and inflammation, which have been identified as critical pathways for development of coronary artery disease, have become easier to diagnose in recent years. Relatively recently, evidence has been found indicating that interactions of the molecular and cellular elements such as matrix metalloproteinases, elements of the immune system, and oxidative stress are involved in the pathophysiology of arterial hypertension. Many studies have revealed several important inflammatory and genetic risk factors associated with CVDs. However, further investigation is crucial to improve our knowledge of CVDs progression and, more importantly, accelerate basic research to improve our understanding of the mechanism of pathophysiology.

MO098HUMAN STOOL METABOLOME DIFFERS UPON 24-HOUR BLOOD PRESSURE LEVELS AND THE NON-DIPPING BLOOD PRESSURE PROFILE

Abstract Background and Aims Dysbiosis of gut microbiota (GM) has been involved in the pathophysiology of arterial hypertension (HT), via a putative role of food-derived short chain fatty acids (SCFAs). Among the clinical manifestations of HT, the absence of a significant drop in blood pressure (BP) overnight (i.e. non-dipping BP profile) has been associated with poor cardiovascular outcomes. The link between GM and non-dipping BP profile is unknown. Method After informed consent, 16 male patients and their female partners (n=10) were subjected to 24-hours ambulatory BP monitoring and were categorized in 2 groups: HT (n=7; 6 men) and normotension (NT) (n=19). According to the conventional night–day systolic BP ratio >0.9, 15 individuals (8 men and 7 women) were categorized as non-dippers. Metabolomics using Nuclear Magnetic Resonance was performed on stool samples, including the quantification of the 3 main SCFAs (i.e. acetate, propionate and butyrate). Results Multivariate analysis (principal component analyses (PCA) and partial least squares (PLS-DA)) of stool metabolomics were not able to statistically separate HT versus NT groups. However, this approach discriminated dippers versus non-dippers groups in both male and female cohorts (Q²=0.87 and 0.98, respectively), as well as in the entire cohort (Q²=0.68). As previously described, fecal amounts of acetate, propionate and butyrate were higher in HT patients than in NT patients in the entire cohort (p=0.027; p=0.015 and p=0.015, respectively). Fecal amounts of acetate, propionate and butyrate were also significantly higher in non-dippers versus dippers in the entire cohort (p=0.027; p=0.038 and p=0.036, respectively). Significant correlations between stool metabolomes and the 24h-mean BP levels were found in male and female cohorts (R²=0.63 and 0.79 respectively) as well as in the entire cohort (R²=0.54). Conclusion In conclusion, this 26-patient cohort highlights significant correlations between stool metabolome and (i) BP levels and (ii) non-dipping BP profile in both men and women.

Human Stool Metabolome Differs upon 24 h Blood Pressure Levels and Blood Pressure Dipping Status: A Prospective Longitudinal Study.

Dysbiosis of gut microbiota (GM) has been involved in the pathophysiology of arterial hypertension (HT), via a putative role of short chain fatty acids (SCFAs). Its role in the circadian regulation of blood pressure (BP), also called “the dipping profile”, has been poorly investigated. Sixteen male volunteers and 10 female partners were subjected to 24 h ambulatory BP monitoring and were categorized in normotensive (NT) versus HT, as well as in dippers versus non-dippers. Nuclear magnetic resonance (NMR)-based metabolomics was performed on stool samples. A 5-year comparative follow-up of BP profiles and stool metabolomes was done in men. Significant correlations between stool metabolome and 24 h mean BP levels were found in both male and female cohorts and in the entire cohort (R2 = 0.72, R2 = 0.79, and R2 = 0.45, respectively). Multivariate analysis discriminated dippers versus non-dippers in both male and female cohorts and in the entire cohort (Q2 = 0.87, Q2 = 0.98, and Q2 = 0.68, respectively). Fecal amounts of acetate, propionate, and butyrate were higher in HT versus NT patients (p = 0.027; p = 0.015 and p = 0.015, respectively), as well as in non-dippers versus dippers (p = 0.027, p = 0.038, and p = 0.036, respectively) in the entire cohort. SCFA levels were significantly different in patients changing of dipping status over the 5-year follow-up. In conclusion, stool metabolome changes upon global and circadian BP profiles in both genders.

HUMAN STOOL METABOLOMES DIFFER UPON 24-HOUR BLOOD PRESSURE LEVELS AND THE NON-DIPPING BLOOD PRESSURE PROFILE

Objective: Dysbiosis of gut microbiota (GM) has been implicated in the pathophysiology of arterial hypertension (HT), via a putative role of food-derived short chain fatty acids (SCFAs) and other metabolites. Among the clinical manifestations of HT, the absence of a significant drop in blood pressure (BP) overnight (i.e. the non-dipping BP profile) has been associated with poor cardiovascular outcomes. The link between GM and the non-dipping BP profile is unknown. Design and method: After informed consent, 16 male patients (mean age = 52.3 ± 12.4 years; 1 patient under beta blocker) and their female partners (n = 10; mean age = 46.5 ± 13.2 years; 1 patient under thiazide diuretic and angiotensin-converting-enzyme inhibitor) were subjected to 24-hour ambulatory BP monitoring and categorized in 2 groups: HT (n = 6 men and 1 woman) and normotension (n = 19). According to the conventional night/day BP ratio >0.9, 15 individuals (n = 8 men and 7 women) were categorized as non-dippers. Metabolomics using Nuclear Magnetic Resonance was performed on stool samples, including the quantification of the 3 main SCFAs (i.e. acetate, propionate and butyrate). Results: Principal component analyses (PCA) discriminated HT versus normotensive individuals on the basis of the stool metabolomes of the entire cohort (Q2 = 0.10). PCA also discriminated dippers versus non-dippers upon the stool metabolomes of the male and female cohorts (Q2 = 0.76 and 0.98, respectively) or the entire cohort (Q2 = 0.27). Significant correlations between stool metabolomes and the mean 24-hour BP levels were highlighted in male and female cohorts (R2 = 0.63 and 0.79, respectively), as well as in the entire cohort (R2 = 0.54). Interestingly enough, a higher variation between stool metabolomes (represented by the measure of inertia) was found in couples with a different BP status (51.4% of inertia) compared to the couples in whom both individuals presented with the same BP status (37.5% of inertia). The propionate/butyrate ratio was higher in the stools of male HT patients versus male normotensive patients (p = 0.03), but no difference was observed in the female cohort or in the entire cohort. Conclusions: In conclusion, this 26-patient cohort highlights significant correlations between the stool metabolome and (i) BP levels and (ii) the non-dipping BP profile in both genders.

Сравнительный анализ блокаторов рецепторов ангиотензина и ингибиторов ангиотензин-превращающего фермента в лечении артериальной гипертензии (обзор литературы)

Cardiovascular diseases are still one of the main causes of death and disability among the adult population, the search for optimal pharmacotherapy of arterial hypertension remains an urgent task. The renin-angiotensin-aldosterone system (RAAS) plays a direct role in the pathophysiology of arterial hypertension, being responsible for regulating fluid volume and maintaining water - salt balance. RAAS is also responsible for the processes of tissue growth and differentiation, apoptosis, and affects the synthesis of many neurohumoral factors. By increasing the activity of the RAAS angiotensin II contributes to vasoconstriction, increased secretion of aldosterone and the activity of the sympathetic nervous system, which in turn leads to the development and progression of hypertension. Angiotensin–II receptor blockers (ARBs) block the AT1 subtype receptors of the same name, which is accompanied by vasodilation, a decrease in the secretion of vasopressin and aldosterone. RAAS blockade is an effective modern reliable way to control blood pressure, as well as prevent related complications. angiotensin converting enzyme inhibitors and angiotensin receptor blockers have similar hypotensive effects and a high safety profile. Due to differences in the mechanism of action, when taking angiotensin receptor blockers, the frequency of undesirable side effects is recorded less, and, accordingly, adherence to treatment is greater. One of the modern angiotensin receptor blockers, olmesartan in various studies has demonstrated its superiority over angiotensin-converting enzyme inhibitors (ramipril and perindopril) in the treatment of arterial hypertension. Olmesartan has proven itself both in monotherapy and in combination with a dihydropyridine calcium channel blocker or a thiazide diuretic.

Biological Context Linking Hypertension and Higher Risk for COVID-19 Severity.

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represents a public health crisis of major proportions. Advanced age, male gender, and the presence of comorbidities have emerged as risk factors for severe illness or death from COVID-19 in observation studies. Hypertension is one of the most common comorbidities in patients with COVID-19. Indeed, hypertension has been shown to be associated with increased risk for mortality, acute respiratory distress syndrome, need for intensive care unit admission, and disease progression in COVID-19 patients. However, up to the present time, the precise mechanisms of how hypertension may lead to the more severe manifestations of disease in patients with COVID-19 remains unknown. This review aims to present the biological plausibility linking hypertension and higher risk for COVID-19 severity. Emphasis is given to the role of the renin-angiotensin system and its inhibitors, given the crucial role that this system plays in both viral transmissibility and the pathophysiology of arterial hypertension. We also describe the importance of the immune system, which is dysregulated in hypertension and SARS-CoV-2 infection, and the potential involvement of the multifunctional enzyme dipeptidyl peptidase 4 (DPP4), that, in addition to the angiotensin-converting enzyme 2 (ACE2), may contribute to the SARS-CoV-2 entrance into target cells. The role of hemodynamic changes in hypertension that might aggravate myocardial injury in the setting of COVID-19, including endothelial dysfunction, arterial stiffness, and left ventricle hypertrophy, are also discussed.

Genetic forms and pathophysiology of essential arterial hypertension in minor indigenous peoples of Russia

BackgroundTo study the genetic forms and pathophysiology of arterial hypertension by evaluating plasma renin activity in the Shors, minor indigenous peoples inhabiting the south of Western Siberia.MethodsA single-stage study of indigenous (the Shors) and non-indigenous peoples living in the villages of Gornaya Shoria of the Kemerovo region in the south of Western Siberia was conducted in the period from 2013 to 2017. One thousand four hundred nine adults (901 Shors and 508 non-indigenous inhabitants) were recruited in the study using a continuous sampling plan. Arterial blood pressure was measured according to 2018 ESC/ESH guidelines for the management of arterial hypertension. All the respondents underwent clinical and instrumental examination. Plasma renin activity was determined by enzyme-linked immunoassay with the BRG kits (Germany). Polymorphisms of ACE (I/D, rs 4340), АGT (c.803 T > C, rs699), AGTR1 (А1166С, rs5186), ADRB1 (с.145A > G, Ser49Gly, rs1801252) and ADRA2B (I/D, rs 28,365,031) genes were tested using polymerase chain reaction.ResultsRenin-dependent hypertensive patients prevailed in both ethnic groups (65.6% in the indigenous group vs. 89.8% in the non-indigenous group, p = 0.001). Prevalence of a volume-dependent AH was low in both groups (34.4% in the indigenous group vs. 10.2% in the non-indigenous group, р = 0.001). The D/D and Т/Т genotypes of the АСЕ [OR = 6.97; 95% CI (1.07–55.58)] and AGT [OR = 3.53; 95% CI (1.02–12.91)] genes were associated with the renin-dependent AH in the Shors. The C/C genotype of AGTR1 gene was found to predispose to the volume-dependent AH [OR = 5.25; 95% CI (1.03–27.89)]. The C/C genotype of AGTR1 gene was associated with moderate or high renin levels suggesting essential AH in the non-indigenous group [OR = 5.00; 95% CI (1.21–22.30), р = 0.029].ConclusionAn in-depth understanding of AH pathophysiology and its genetic forms ensures the optimal choice of blood pressure-lowering treatment and optimizes AH control.

Altered renal medullary blood flow: A key factor or a parallel event in control of sodium excretion and blood pressure?

In the context of the ongoing debate on the mechanism of blood pressure (BP) regulation and pathophysiology of arterial hypertension ("renocentric" vs "neural" concepts), attention is focused on the putative regulatory role of changes in renal medullary blood flow (MBF). Experimental evidence is analysed with regard to the question whether an elevation of BP and renal perfusion pressure (RPP) is likely to increase MBF due to its impaired autoregulation. It is concluded that such increases have been clearly documented only in rats with extracellular fluid volume expansion. A possible translation of this finding to BP regulation in health and hypertension in humans may only be a matter of speculation. Within the "renocentric" theory, the key event leading to restoration of initial BP level is pressure natriuresis. Its relation to elevation of renal interstitial hydrostatic pressure and to the phenomenon of "wash-out" of renal medullary solutes by increasing MBF is discussed. We also assessed the validity of data supporting the putative mechanism of short-term restoration of elevated BP owing to the release of a vasodilator lipid (medullipin) by the medulla. The structure of the proposed medullary lipid is still undefined, and there is no sound evidence on its mediatory role in lowering elevated BP level. In conclusion, MBF change can hardly be regarded as a crucial event in the regulation of BP: it can be involved in the control of sodium excretion and BP only in some circumstances, although its contributory role cannot be excluded.

Hypertension in Chronic Kidney Disease: Novel Insights.

Management of arterial hypertension in patients with chronic kidney disease (CKD) remains a major challenge due to its high prevalence and associations with cardiovascular disease (CVD) and CKD progression. Several clinical trials and meta-analyses have demonstrated that aggressive treatment of hypertension in patients with and without CKD lowers the risk of CVD and all-cause mortality, nevertheless the effects of blood pressure (BP) lowering in terms of renal protection or harm remain controversial. Both home and ambulatory BP estimation have shown that patients with CKD display abnormal BP patterns outside of the office and further investigation is required, so as to compare the association of ambulatory versus office BP measurements with hard outcomes and adjust treatment strategies accordingly. Although renin-angiotensin system blockade appears to be beneficial in patients with advanced CKD, especially in the setting of proteinuria, discontinuation of renin-angiotensin system inhibition should be considered in the setting of frequent episodes of acute kidney injury or hypotension while awaiting the results of ongoing trials. In light of the new evidence in favor of renal denervation in arterial hypertension, the indications and benefits of its application in individuals with CKD need to be clarified by future studies. Moreover, the clinical utility of the novel players in the pathophysiology of arterial hypertension and CKD, such as microRNAs and the gut microbiota, either as markers of disease or as therapeutic targets, remains a subject of intensive research.

Prevention of Cardiovascular Disease: Screening for Magnesium Deficiency.

Magnesium is an essential mineral naturally present in the human body, where it acts as cofactor in several enzymatic reactions. Magnesium is a key cardiovascular regulator, which maintains electrical, metabolic, and vascular homeostasis. Moreover, magnesium participates in inflammation and oxidative processes. In fact, magnesium deficiency is involved in the pathophysiology of arterial hypertension, diabetes mellitus, dyslipidemia, metabolic syndrome, endothelial dysfunction, coronary artery disease, cardiac arrhythmias, and sudden cardiac death. In consideration of the great public-health impact of cardiovascular disease, the recognition of the negative effects of magnesium deficiency suggests the possible role of hypomagnesaemia as cardiovascular risk factor and the use of serum magnesium level for the screening and prevention of cardiovascular risk factors and cardiovascular diseases. Moreover, it might help with the identification of new therapeutical strategies for the management of cardiovascular disease through magnesium supplementation.

Arterial hypertension in children after aortic coarctation repair: current challenges for diagnostics and treatment

Coarctation of the aorta is a well-studied congenital heart disease. Our understanding of this congenital heart disease evolves every year from simple obstructive aortic lesions to systemic dysfunction of the cardiovascular system. In the past two decades, there has been a progressive decrease in mortality and early postoperative complications of newborns and infants with aortic coarctation. However, these patients with coarctation of aorta have a high risk of postoperative complications in the long-term period, despite successful correction at an early age. This review will focus on the issues mainly related to blood pressure. Arterial hypertension has been reported to occur in up to 90% of patients, and is considered as the main cause of premature cardiovascular diseases. The development of arterial hypertension in patients after correction of aortic coarctation is likely to be multifactorial and may be associated with the changes in elastic properties of the aorta wall, presence of residual obstruction, changes in the aortic arch geometry, immune-inflammatory disorders and changes in the regulation of renin-angiotensin and baroreceptors. Also described are the prevalence and pathophysiology of arterial hypertension in children who have undergone aortic coarctation repair. Due attention is given to the issues of accurate blood pressure measurement at an early stage of arterial hypertension. Although the patterns for diagnostics of arterial hypertension in adults are well established, we highlight the issues of premature cardiovascular events development in children and describe the techniques, which help provide complementary information for cardiovascular assessment in this group of patients. Received 7 August 2018. Revised 6 December 2018. Accepted 10 December 2018. AcknowledgmentWe would like to express our gratitude to Sergey M. Ivantsov for technical support. Funding: The study did not have sponsorship. Conflict of interest: Authors declare no conflict of interest.

Renin Inhibition with Aliskiren: A Decade of Clinical Experience.

The renin-angiotensin-aldosterone system (RAAS) plays a key role in the pathophysiology of arterial hypertension as well as in more complex mechanisms of cardiovascular and renal diseases. RAAS-blocking agents like angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers, have long been key components in the treatment of essential hypertension, heart failure, diabetic nephropathy, and chronic kidney disease, showing benefits well beyond blood pressure reduction. Renin blockade as the first step of the RAAS cascade finally became possible in 2007 with the approval of aliskiren, the first orally active direct renin inhibitor available for clinical use and the newest antihypertensive agent on the market. In the last decade, many clinical trials and meta-analyses have been conducted concerning the efficacy and safety of aliskiren in comparison to other antihypertensive agents, as well as the efficacy and potential clinical use of various combinations. Large trials with cardiovascular and renal endpoints attempted to show potential benefits of aliskiren beyond blood pressure lowering, as well as morbidity and mortality outcomes in specific populations such as diabetics, heart failure patients, and post-myocardial infarction individuals. The purpose of this review is to present the currently available data regarding established and future potential clinical uses of aliskiren.

Recent advances in the pathophysiology of arterial hypertension: potential implications for clinical practice.

Hypertension remains a major and growing public health problem associated with the greatest global rate of cardiovascular morbidity and mortality. Although numerous factors contribute to poor control of blood pressure (BP) and to pseudoresistance (eg, unawareness, lifestyle habits, nonadherence to medication, insufficient treatment, drug‑induced hypertension, undiagnosed secondary causes), true resistant hypertension (RH) is reported in 10.1% of patients treated for elevated BP. While the mechanisms underlying RH remain complex and not entirely understood, sympathetic activation involved in the pathophysiology of hypertension, disease progression, and adverse complications is further augmented in patients with drug‑resistant hypertension. The well‑established contribution of neurogenic component of hypertension has led to the introduction of new alternative therapies aimed specifically at modulating central and neural reflexes mechanisms involved in BP control. Although clinical benefits of lowering BP with renal denervation, baroreflex activation therapy, carotid body denervation, central arteriovenous anastomosis, and deep brain stimulation have advanced our knowledge on uncontrolled hypertension, the variable BP response has prompted extensive ongoing research to define predictors of treatment effectiveness and further investigation of pathophysiology of RH. Very recently, research on the role of vasopressinergic neurons, masked tachycardia, and impaired brain neural activity has provided novel insights into hypertension. This review briefly summarizes the role of the centrally mediated sympathetic nervous system in hypertension, the therapeutic strategies that distinctively target impaired neural reflex mechanisms, and potential implications for future clinical research and therapies.

Increased mobilization of mesenchymal stem cells in patients with essential hypertension: the effect of left ventricular hypertrophy.

Stem cells have great clinical significance in many cardiovascular diseases. However, there are limited data regarding the involvement of mesenchymal stem cells (MSCs) in the pathophysiology of arterial hypertension. The aim of this study was to investigate the circulation of MSCs in patients with essential hypertension. The authors included 24 patients with untreated essential hypertension and 19 healthy individuals. Using flow cytometry, MSCs in peripheral blood, as a population of CD45-/CD34-/CD90+ cells and also as a population of CD45-/CD34-/CD105+ cells, were measured. The resulting counts were translated into the percentage of MSCs in the total cells. Hypertensive patients were shown to have increased circulating CD45-/CD34-/CD90+ compared with controls (0.0069%±0.012% compared with 0.00085%±0.0015%, respectively; P=.039). No significant difference in circulating CD45-/CD34-/CD105+ cells was found between hypertensive patients' and normotensive patients' peripheral blood (0.018%±0.013% compared with 0.015%±0.014%, respectively; P=.53). Notably, CD45-/CD34-/CD90+ circulating cells were positively correlated with left ventricular mass index (LVMI) (r=0.516, P<.001). Patients with essential hypertension have increased circulating MSCs compared with normotensive patients, and the number of MSCs is correlated with LVMI. These findings contribute to the understanding of the pathophysiology of hypertension and might suggest a future therapeutic target.