Pathogenesis Of Primary Hypertension Research Articles

Dysfunction of M channels in the insular cortex is involved in pathogenesis of primary hypertension

Heightened sympathetic nerve activity is critically involved in the pathogenesis of primary hypertension. However, the sources driving increased sympathetic vasomotor tone remain unclear. The posterior insular cortex (PIC) is a brain region involved in regulating blood pressure and sympathetic tone. Neurons in the PIC project to the rostral ventrolateral medulla (RVLM), a key brain stem region in regulating sympathetic nerve activity and blood pressure. The non-inactivating voltage-dependent K+ channels, M channels (Kv7/KCNQ channel family) encoded by KCNQ2/3 genes, play a unique role in stabilizing the neuronal membrane potential and regulating neuronal excitability. Here, we determined if the M channel activity of neurons in the PIC is altered in a primary hypertension. Compared with Wistar-Kyoto (WKY) rats, the mRNA and protein expression levels of Kv7.2/Kv7.3 in the PIC tissue were significantly reduced in spontaneously hypertensive rats (SHRs). Microinjection of M channel blocker 10, 10-bis (4-pyridinylmethyl)-9(10H)-anthracnose (XE-991) into the PIC increased arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA) in anesthetized WKY rats, while induced minimal changes of ABP and RSNA in SHRs. M currents recorded from PIC neurons in brain slices labeled by retrograde tracer, Fluospheres, injected into the RVLM were significantly smaller in SHRs than in WKY rats. Furthermore, bath application of specific M channel blocker XE-991 increased the firing rate of PIC-RVLM output neurons in WKY rats while caused a minimal increase in firing rate of PIC-RVLM output neurons in SHRs. In addition, M currents recorded from PIC-RVLM output neurons in SHRs were significantly smaller than those recorded from WKY rats. These data suggest that M channel activity is diminished in PIC-RVLM output neurons in SHRs, and the diminished Kv7 channel activity contributes to elevated sympathetic outflow in primary hypertension. This novel information provides new a mechanistic insight into the pathogenesis of neurogenic hypertension. Supported by grants from National Institutes of Health (HL139523, HL142133, and HL159157 to DPL). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

THE SUBCLINICAL INFLAMMATION IN PEDIATRIC PATIENTS WITH PRIMARY HYPERTENSION AND WHITE COAT HYPERTENSION

Objective: Adult and experimental data indicate the vital role of inflammation in the pathogenesis of primary hypertension. The study aimed to evaluate subclinical inflammation in patients with primary hypertension (PH) and white coat hypertension (WCH). Design and method: In 56 untreated pediatric patients with PH, 40 with WCH, and 30 healthy individuals (CG – control group), we evaluated high sensitivity C-reactive protein (hsCRP), interleukin 18 (IL18) concentrations, complete blood count-derived markers of inflammation, office and ambulatory blood pressure, and selected clinical and biochemical parameters. Results: hsCRP was significantly higher in PH patients compared to CG (PH vs. CG: 4.9±5.2 vs. 2.8±5.4 [mg/dL], p=0.002), and neutrophil and monocyte counts were significantly higher in PH and WCH patients compared to CG (PH vs. WCH vs. CG, neutrophils: 3.89±1.44 vs. 3.40±1.75 vs. 2.63±0.96 [∗10^3/μL], p=0.001, monocytes: 0.56±0.17 vs. 0.53±0.18 vs. 0.46±0.14 [∗10^3/μL], p=0.026). Receiver operating characteristic analysis revealed good prognostic profiles for hsCRP (area under curve [AUC]=0.668, p=0.0005), neutrophil (AUC=0.691, p=0.0001), lymphocyte (AUC=0.615, p=0.0230), monocyte (AUC=0.622, p=0.0148), and platelet counts (AUC=0.606, p=0.0364), as well as the neutrophil-to-lymphocyte ratio (AUC=0.619, p=0.0181), monocyte-to-neutrophil ratio (MNR) (AUC=0.617, p=0.0204), and platelet-to-mean platelet volume ratio (AUC=0.606, p=0.0370) as predictors of the presence of primary hypertension. In multivariate analysis monocyte-to-lymphocyte ratio (MLR) and platelet count (beta=0.217, p=0.011; beta=0.191, p=0.036) were significant predictors of office diastolic blood pressure Z-score, neutrophil count predicted 24h systolic blood pressure Z-score (beta=0.365, p=0.005); MLR, lymphocyte count, IL-18, and MNR predicted 24 h diastolic blood pressure Z-score (beta=0.305, p=0.002; beta=0.253, p=0.010; beta=-0.197, p=0.019; beta=-0.189, p=0.029), and neutrophil count together with IL-18 predicted 24h mean arterial pressure Z-score (beta=0.210, p=0.027; beta=-0.209, p=0.012). Conclusions: 1.Patients with primary hypertension and white coat hypertension are characterized by similar levels of subclinical inflammation, significantly higher compared to healthy peers. 2. Complete blood count-derived indices, especially neutrophil count and MLR, can be an important adjunct to the clinical evaluation of pediatric patients with primary hypertension.

Assessment of serum concentrations of matrix metalloproteinases-2, -3 and -9, and tissue inhibitor of metalloproteinases-1 in children with primary hypertension

Introduction: Primary hypertension is regarded to be a growing health concern in children. The pathogenesis of primary hypertension is multifactorial. The role of altered levels of matrix metalloproteinases has been proposed. In hypertension, metalloproteinases are engaged not only in vascular remodelling but also in activation of vasoconstrictive agents. Aim of the study: We aimed at comparing the serum concentrations of matrix metalloproteinases-2, -3 and -9, and tissue inhibitor of metalloproteinases-1 in children with primary hypertension and normotensive peers. Materials and methods: We surveyed 23 children with primary hypertension, aged 14.75 years (median; interquartile range, IQR 3.66) and 23 normotensive subjects, aged 14.66 years (median; IQR 6.25). Serum concentrations of matrix metalloproteinases-2, -3 and -9, and tissue inhibitor of metalloproteinases-1 were measured using enzyme-linked immunosorbent method, and the scores were compared with Mann–Whitney U test, with the level of significance at p ≤ 0.05. Results: In children with primary hypertension, serum concentration of matrix metalloproteinase-2 [178.1 (IQR: 35.84) vs. 99.9 (IQR: 20.1) ng/mL], -3 [6.47 (IQR: 1.75) vs. 2.67 (IQR: 1.08) ng/mL], -9 [191.1 (IQR: 52.75) vs. 58.34 (IQR: 18.99) ng/mL] and tissue inhibitor of metalloproteinases-1 [863.9 (IQR: 192.9) vs. 335.41 (IQR: 109.99) ng/mL] were significantly higher than in the normotensive controls (p < 0.00001). Matrix metalloproteinase-9/tissue inhibitor of metalloproteinases-1 ratio [0.22 (IQR: 0.1) vs. 0.18 (IQR: 0.05)] was also significantly elevated in the hypertensive participants (p = 0.008). Conclusions: Elevated serum concentrations of matrix metalloproteinases-2, -3 and -9, and tissue inhibitor of metalloproteinases-1 in children with primary hypertension may indicate their role in the development of hypertension and/or on the presence of vascular remodelling at an early stage of the disease.

INCREASED IONIZED CALCIUM-MAGNESIUM-RATIO IN ELDERLY HYPERTENSIVES - RELATIONSHIP TO ARTHERIOSCLEROSIS

Objective: Changes in calcium and magnesium metabolism are involved in the pathogenesis of primary hypertension. The calcium and magnesium flux across the external membrane is regulated by a calcium pump (calcium-magnesium-ATPase), calcium and magnesium channels (TRPM 6 and 7) and a sodium-magnesium-antiport. An increased calcium-magnesium-ratio is known to be involved in the development of atherosclerosis. Early onset of these disorders are known in hypertension. In earlier animal studies this phenomenon has been described, too. Design and method: Our study was performed in 18 elderly hypertensives (9 male/9 female, with normal renal function, age beyond 60 years). No patient had diabetes mellitus, no diuretic therapy for at least 4 weeks before entry in study and no magnesium supplementation. In each patient ionized calcium and magnesium was measured and the calcium-magnesium-ratio was calculated. Measurements were performed by a Prime Plus Apparatus by NOVA Medical, Rödermark, Germany. Results: Ionized magnesium was measured 0.55 + /-0.04 mmol/L, normal range 0.54–0.80 mmol/L) in patients. The ionized calcium-magnesium-ratio was 2.33+/-0.18 (normal range below 2.40). About 40% of elderly hypertensives showed an increased ratio of ionized calcium and magnesium, which is known to be a marker for the development of artheriosclerosis. Conclusions: As described earlier, a magnesium deficiency can be involved in the pathogenesis of hypertension and in elderly. The increased calcium-magnesium-ratio is also a pathogenetic factor for artheriosclerosis often found in elderly hypertensives with vascular damage, e.g. stroke, renal insufficiency or heart disease.

Circulating Levels of Endothelin-1 and Big Endothelin-1 in Patients with Essential Hypertension.

The role of endothelin-1 (ET-1) in the pathogenesis of hypertension (HTN) is not clearly established. There is evidence that its circulating levels are elevated in some forms of experimental and human HTN, but this was not a consistent finding. Based on these controversial data, we tested serum levels of ET-1 and Big ET-1 (the precursor of ET-1) in patients with essential HTN, comparing the results with those of healthy normotensive controls. The levels of ET-1 and Big ET-1 were measured by ELISA. Our results in patients with essential HTN showed that the mean levels of ET-1 (5.01 ± 2.1 pg/mL) were significantly higher (F = 6.34, p = 0.0144) than the mean levels in the control group (3.2 ± 1.0 pg/mL). The levels of Big ET-1 in patients with essential HTN (0.377 ± 0.1 pmol/L) were similar to those in the control group (0.378 ± 0.07 pmol/L) and did not differ significantly (F = 0.00, p = 0.9531). These data suggest that ET-1, but not Big ET-1, may play an important role in the pathogenesis of primary HTN.

Diet-dependent acid load is associated with mean arterial pressure in a cohort of non-obese, non-black, postmenopausal women.

Higher sodium (Na+) intake is associated with higher blood pressure (BP). Whether this relationship is stronger with diet-dependent acid load (DAL) and in patients diagnosed with hypertension or normal BP is not well determined. We studied 170 postmenopausal women randomized to receive potassium bicarbonate or placebo for 36months, after which 24-hour urine and arterialized blood samples were collected. We investigated the association between DAL estimated as urinary potential renal acid load (UPRAL) and mean arterial pressure (MAP) using a mixed-effects model, adjusting for age, anthropometrics, creatinine clearance, and treatment. Adjusted regression estimates for changes in Na+ and UPRAL on MAP after 12months of follow-up were calculated, and further adjustments were made for changes in potassium (K+) and body mass index (BMI). MAP was inversely associated with UPRAL (β [95%confidence interval]: -0.11[-0.25, -0.001]). There was an effect modification by hypertension (p-interaction = 0.04); MAP decreased significantly in normotensives, but the association was not significant in hypertensives. A decrease of 0.70mmHg in MAP [0.13, 1.69] per 50 mmol/24 hour reduction in Na+ was noted when the model was adjusted for change in K+. Our results with UPRAL exhibited a stronger dose-response for MAP, which remained significant after adjusting for BMI. UPRAL was independently associated with MAP even after adjusting for potential confounders, and the data showed that this association was more pronounced in normotensive patients. Novelty: First longitudinal study on the association of UPRAL and MAP. Association was a more robust relationship than that between U[Na+/K+] ratio and MAP. UPRAL may play a significant role in the pathogenesis of primary hypertension.

ARTERIAL STIFFNESS AND LOW-GRADE INFLAMMATION IN CHILDREN WITH PRIMARY HYPERTENSION

Abstract Objective: In last years, numerous associations between immune system and pathogenesis of primary hypertension (PH) have been revealed. Also, experimental and adult data suggest that inflammation plays a major role in arteries stiffening. The aim of the study was to assess relation between low-grade inflammation and arterial damage in children with PH. Design and method: In the group of 119 pediatric patients with PH (14.94 ± 2.76 years, 86 boys, 33 girls) and 45 healthy children (14.91 ± 2.69 years, 27 boys, 18 d girls) we analyzed parameters of low-grade inflammation: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and mean platelet volume (MPV), peripheral office blood pressure, ABPM, central blood pressure, parameters of arterial damage: aortic pulse wave velocity (aPWV) [m/s], [Z-score], augmentation index (AIx75HR [%]), common carotid artery intima media thickness (cIMT) [mm], [Z-score], carotid artery stiffness (E-tracking), and clinical and biochemical parameters. Results: Children with PH had higher NLR (1.93 ± 1.52 vs. 1.32 ± 0.44, p = 0.010), PLR (131.39 ± 41.87 vs. 114.68 ± 37.60, p = 0.020), MAP 24 h Z-score in ABPM (1.34 ± 1.38 vs. 0.43 ± 0.49, p = 0.002), aortic systolic blood pressure (AoSBP) (110.44 ± 9.95 vs. 101.50 ± 8.99 [mm Hg], p < 0.001), aPWV (5.36 ± 0.88 vs. 4.88 ± 0.92 [m/s], p = 0.004) and cIMT (0.46 ± 0.07 vs. 0.43 ± 0.07 [mm], p = 0.002) compared to healthy children. In children with PH NLR correlated (p < 0.05) positively with systolic, diastolic, and mean blood pressure in ABPM (r = 0,24, r = 0,22, r = 0,25), with aPWV [m/s], [Z-score] (r = 0,24, r = 0,20) and pulse wave velocity in carotid artery (PWVbeta) [m/s] (r = 0.20); no such correlations were found in healthy children. NLR, PLR, and MPV did not correlate with cIMT, age, and sex in either of the groups. Conclusions: In pediatric patients with primary hypertension arterial stiffness is related to degree of low-grade

URIC ACID IN PEDIATRIC PATIENTS WITH PRIMARY HYPERTENSION

Abstract Objective: Increased concentration of uric acid may play a role in the pathogenesis of primary hypertension (PH). Aim of the study was to assess concentration of uric acid and its correlation with selected clinical and biochemical parameters in children with PH. Design and method: In a group of 57 untreated pharmacologically children with PH (44 boys, 13 girls, mean age 14.99 ± 2.84 years) following parameters were assessed: serum uric acid concentration [mg/dL], blood pressure in office measurement and in 24-hour ambulatory blood pressure monitoring, and selected clinical and biochemical parameters. Control group consisted of 20 healthy children (mean 14.11 ± 2.99 years). Results: Serum uric acid concentration was significantly higher in children with PH compared to healthy children (5.72 ± 1.38 vs. 4.55 ± 1.07 [mg/dL]; p = 0.001). In patients with PH, its concentration was significantly higher in boys compared to girls ((6.12 ± 1.20 mg/dL vs. 4.35 ± 1.13 mg/dL, p < 0.001), no such difference was found in healthy children. In the PH group, uric acid concentration correlated positively with age (r = 0.426, p = 0.001), height (r = 0.557, p < 0.001), weight (r = 0.518, p < 0.001), weight Z- score (r = 0.296, p = 0.025), BMI (r = 0.316, p = 0.017), neutrophil count (r = 0.280, p = 0.035), systolic blood pressure (r = 0.375, p = 0.004) and pulse pressure (r = 0.444, p = 0.001) in ABPM and negatively with HDL cholesterol, heart rate (r = -0.310, p = 0.02 (1 = -0.309, p = 0.020) and nighttime diastolic blood pressure dip (r = -0.268, p = 0.044) in ABPM. In multivariate analysis, the determinants of uric acid concentration in children with PH were sex (beta = 0,367, 95%CI (0.122–0.611), p = 0.004) and weight Z-score (beta = 0.254, 95%CI (0.005–0.504), p = 0.046). Conclusions: Children with primary hypertension have increased serum uric acid concentration compared to healthy children. The risk factors for hyperuricemia in pediatric patients with primary hypertension are male sex and high body weight.

Uric Acid and Hypertension: An Update With Recommendations.

The association between increased serum urate and hypertension has been a subject of intense controversy. Extracellular uric acid drives uric acid deposition in gout, kidney stones, and possibly vascular calcification. Mendelian randomization studies, however, indicate that serum urate is likely not the causal factor in hypertension although it does increase the risk for sudden cardiac death and diabetic vascular disease. Nevertheless, experimental evidence strongly suggests that an increase in intracellular urate is a key factor in the pathogenesis of primary hypertension. Pilot clinical trials show beneficial effect of lowering serum urate in hyperuricemic individuals who are young, hypertensive, and have preserved kidney function. Some evidence suggest that activation of the renin-angiotensin system (RAS) occurs in hyperuricemia and blocking the RAS may mimic the effects of xanthine oxidase inhibitors. A reduction in intracellular urate may be achieved by lowering serum urate concentration or by suppressing intracellular urate production with dietary measures that include reducing sugar, fructose, and salt intake. We suggest that these elements in the western diet may play a major role in the pathogenesis of primary hypertension. Studies are necessary to better define the interrelation between uric acid concentrations inside and outside the cell. In addition, large-scale clinical trials are needed to determine if extracellular and intracellular urate reduction can provide benefit hypertension and cardiometabolic disease.

Down-regulation of miRNA 145 and up-regulation of miRNA 4516 may be associated with primary hypertension.

Complex mechanisms including genetic factors have been proposed in the pathogenesis of primary hypertension (HT). Micro RNAs (miRNAs) are single-stranded RNA molecules that are not converted into protein products. However, it has been established that genes regulate conversion into protein products. The primary aim of this study was to investigate the roles of miRNA 4516, miRNA 145, miRNA 24, and miRNA 181a in the pathogenesis of HT. The secondary aim was to investigate the relation between these miRNAs and renin, aldosterone, norepinephrine, renalase, and NOS. Fifty-two hypertensive and 51 control normotensive individuals under observation in the Cappadocia cohort were included in the study. miRNA 4516, miRNA 181a, miRNA 24, and miRNA 145 levels were measured using the ddPCR method. miRNA 4516 and norepinephrine levels were significantly higher in the HT group (P<.005 for both), while miRNA 145 levels were significantly lower (<.05). miRNA 4516 up-regulation (P<.05) and miRNA 145 down-regulation (P<.05) were identified as independent predictors of HT. Renalase exhibited negative correlation with miRNA 4516 and positive correlation with miRNA 145 in the patient and control group. In addition, negative correlation was present between miRNA 24 and NE and NOS and between miRNA 181a and NOS in the patient group. Our study identified, for the first time in the literature, miRNA 4516 up-regulation and miRNA 145 down-regulation as independent determinants of HT. Further studies performed in the light of our findings may lead to a better understanding of the pathogenesis and new therapeutic possibilities.

LDL cholesterol is associated with systemic vascular resistance and wave reflection in subjects naive to cardiovascular drugs

Background and aim: Low density lipoprotein cholesterol (LDL-C) is a primary risk factor for atherosclerosis, but it is also associated with elevated blood pressure (BP) and future development of hypertension. We examined the relationship between LDL-C and haemodynamic variables in normotensive and never-treated hypertensive subjects.Methods: We recruited 615 volunteers (19–72 years) without lipid-lowering and BP-lowering medication. Supine haemodynamics were recorded using continuous radial pulse wave analysis, whole-body impedance cardiography, and single channel electrocardiogram. The haemodynamic relations of LDL-C were examined using linear regression analyses with age, sex, body mass index (BMI) (or height and weight as appropriate), smoking status, alcohol use, and plasma C-reactive protein, sodium, uric acid, high density lipoprotein cholesterol (HDL-C), triglycerides, estimated glomerular filtration rate, and quantitative insulin sensitivity check index as the other included variables.Results: The mean (SD) characteristics of the subjects were: age 45 (12) years, BMI 27 (4) kg/m2, office BP 141/89 (21/13) mmHg, creatinine 74 (14) µmol/l, total cholesterol 5.2 (1.0), LDL-C 3.1 (0.6), triglycerides 1.2 (0.8), and HDL-C 1.6 (0.4) mmol/l. LDL-C was an independent explanatory factor for aortic systolic and diastolic BP, augmentation index, pulse wave velocity (PWV), and systemic vascular resistance index (p < 0.05 for all). When central BP was included in the model for PWV, LDL-C was no longer an explanatory factor for PWV.Conclusions: LDL-C is independently associated with BP via systemic vascular resistance and wave reflection. These results suggest that LDL-C may play a role in the pathogenesis of primary hypertension.

PP.04.05] ACCELERATED DEVELOPMENT OF IMMUNE CELLS IN CHILDREN WITH PRIMARY HYPERTENSION

Objective: Immune system plays a role in pathogenesis of primary hypertension (PH) and activation of immune cells is associated with subclinical hypertensive arterial injury. One of the markers of maturation of immune cells is increased number and percentage of memory cells. We hypothesized that children with PH have faster maturation of immune cells. Design and method: The distribution of peripheral T cell subsets (CD4+ and CD8+) expressing CD45 common leukocyte antigen (CD45Ag) isoforms: CD45RA (naive cells), CD45RO (memory cells) and CD31 (pecam-1, a marker of early thymic emigrants) was evaluated by three-color flow cytometry in a group of 11 PH adolescents and 16 healthy, age matched controls. Results: Hypertensive children had higher proportion of “memory” CD8 cells (CD8/CD8RO+) than their healthy counterparts (17.0 range: 11.9–23.8 vs 10.9 9.1–14.1; p = 0.03), lower of CD8/CD8RA+ cells (72.3 range: 66.5–81.9 vs 81.6 77.4–84.3; p = 0.05), and lower CD8RA/CD8RO+ ratio than the controls (5.1 range: 2.7–6.9 vs 7.4 5.5–8.9; p = 0.028). Percentage of CD4 and CD8 T bearing “naive” or “memory” phenotype correlated with brachial and aortic pulse pressure. Additionally, CD8RA/RO+ ratio was associated with pulse pressure (p = 0.03, r = −0.337) and aortic pulse pressure (p = 0.03, r = −0.384). There was also negative correlation of percentage of CD4/CD31+ with both absolute and standardized values of carotid wall cross sectional area (p = 0.01, r = −0.433 p = 0.016, r = −0.410, respectively). Conclusions: Adolescents with PH present subtle alterations in maturation of immune system manifested by: a) the decreased number of early thymic emigrants within CD4+ T cell suggesting accelerated thymic senescence, b) the increased population of more mature cells expressing “memory” markers, c) the associations with indirect indices of arterial stiffness and carotid artery remodelling and d) shift towards “memory” phenotype in T cells. Altogether these findings indicate that early stage of human primary hypertension and arterial remodelling may be related to certain defects in T cell development that result in accelerated maturation and senescence of immune system.

The impact of sodium and potassium on hypertension risk.

The pathogenic role of sodium surfeit in primary hypertension is widely recognized but that of potassium deficiency usually has been ignored or at best assigned subsidiary status. Weighing the available evidence, we recently proposed that the chief environmental factor in the pathogenesis of primary hypertension and the associated cardiovascular risk is the interaction of the sodium surfeit and potassium deficiency in the body. Here, we present the major evidence highlighting the relationship between high-sodium intake and hypertension. We then examine the blood pressure-lowering effects of potassium in conjunction with the pernicious impact of potassium deficiency on hypertension and cardiovascular risk. We conclude with summarizing recent human trials that have probed the joint effects of sodium and potassium intake on hypertension and its cardiovascular sequelae. The latter studies lend considerable fresh support to the thesis that the interaction of the sodium surfeit and potassium deficiency in the body, rather than either disturbance by itself, is the critical environmental factor in the pathogenesis of hypertension.

The role of the kidney and the sympathetic nervous system in hypertension

Nearly one-third of the world's population has hypertension. The human and societal impact of hypertension is enormous. Primary hypertension accounts for 95 % of cases of hypertension in adults. The pathogenesis of primary hypertension is complex. The kidney and the sympathetic nervous system play important roles in the development and maintenance of hypertension. This review discusses their respective roles, the interaction between the two, implications of sympathetic overactivity in kidney disease and therapeutic interventions that have been developed on the basis of this knowledge, especially modulation of the sympathetic nervous system.

Determination of Vascular Endothelial Growth Factor (VEGF) and Tie-2 Levels in Patients with Primary Hypertension

PP-027 It has been revealed that many factors can take a part in pathogenesis of primary hypertension. One of these factors is abnormal angiogenesis. In this study we aimed to investigate the levels of VEGF, an angiogenic factor, and Tie-2, angiopoetin receptor, in individuals with hypertension and

Altered Genes Profile of Renin–Angiotensin System, Immune System, and Adipokines Receptors in Leukocytes of Children With Primary Hypertension

Renin-angiotensin system, metabolic abnormalities, and immune activity have a role in the pathogenesis of primary hypertension. We assessed the leukocyte mRNA expression of angiotensinogen, angiotensin converting enzyme, renin, angiotensin 2 type 1 receptor, CD14 molecule, adiponectin type 1 receptor, and leptin receptor in hypertensive children before and after nonpharmacological treatment. Leukocyte mRNA expression was measured by means of quantitative real-time reverse transcriptase-polymerase chain reaction in 23 hypertensive children before and after 6 months of nonpharmacological treatment based on dietary advice and physical activities. Twenty-three normotensive children matched for age, sex, and body mass index served as a control group. Before treatment patients had elevated expression of angiotensin converting enzyme and CD14 mRNA, decreased expression of angiotensinogen and angiotensin type 1 receptor mRNA, and unchanged expression of renin, adiponectin, and leptin receptors mRNA as compared with controls. Renin mRNA negatively correlated with 24-hour mean arterial pressure and carotid intima-media thickness. Six months of nonpharmacological treatment caused decrease of blood pressure and normalization of metabolic abnormalities. Renin, adiponectin, and leptin receptors mRNA expression decreased and were lower than in control group. Changes in blood pressure, left ventricular mass, carotid intima-media thickness, body mass index, and waist circumference did not correlate with changes in the expression of renin-angiotensin system genes, CD14, leptin, and adiponectin receptors mRNA. We conclude that leukocytes of hypertensive children displayed alterations in the expression of renin-angiotensin system genes as well as those of CD14. Nonpharmacological treatment resulted in downregulation of genes involved in renin-angiotensin activation and those engaged in leukocyte responses to adipokines.

The role of T cells in the pathogenesis of primary hypertension

Accumulating evidence indicates that T cells play an important role in the pathogenesis of hypertension. Here we review the investigations that have shown that T cells are infiltrating the kidney in hypertension. Interstitial accumulation of immune cells is associated with increments in oxidative stress and renal angiotensin II activity that result in the impairment in pressure natriuresis. The severity of salt-sensitive hypertension is directly correlated with the intensity of immune cell infiltration in the kidney. Reducing the renal infiltration of T cells prevents or ameliorates hypertension and the induction of tubulointerstitial inflammation results in salt-sensitive hypertension. The potential participation of autoimmune mechanisms in the renal infiltration of immune competent cells is discussed.

Breakthrough Treatment of Hypertension, Hypertension’s “Syndrome X” is now Re-defined.

Objectives: Find and eradicate the root cause/s of Primary & Secondary Hypertension.For a long time, Syndrome X has been regarded as a root cause of primary & secondary Hypertension. The prevailing cause of this ghost syndrome has never been documented, defined or eradicated as yet. However, the patients worldwide are being maintained with a variety of Neuro-electrical (Voltage & Charge) & Vascular (Hemodynamic) manipulative medicine and radically performing the Renal Sympathetic Ablation, to sustain a normal blood pressure. Great many possible parameters have been established to view the existence of the hypertension, Bacterial, Viral Hormonal and anatomical. In the recent years, scientists are looking closely at the Neuroinvasive viruses and their role in the cardiovascular disease. Most scientists agree to a common instigator of the cardiac pathology that anatomically leads to hypertension. The pathological issues can only be resolved by the medical intervention. All conventional treatments provide the symptomatic resolution only. Very little work has been done on the understanding of the Neuro-cardiac pathology induced by herpes family of viruses. The electrical voltage transitional activity can be seen changed, under the influence of the electrolyte imbalance of the myocardium cells i.e. high/ Low Na+ or high/ Low Potassium or Calcium. The pathogenesis of primary hypertension is multifactorial. However, the sympathetic nervous system plays an important role in circulatory and metabolic control and has clearly been established as a major contributor to the development of hypertension, with blood pressure elevation being initiated and sustained by elevated sympathetic nervous activity. Increased sympathetic outflow to the heart resulting in increased cardiac output and neurally mediated vasoconstriction of peripheral blood vessels are obvious examples of neural pathophysiological pathways leading to elevated blood pressure. The consequences of increased sympathetic outflow to the kidneys, perhaps most important in this context are sodium and water retention, increased renin release and alterations of renal blood flow, effects that contribute substantially to blood pressure elevations both acutely and in the long term. Accordingly, targeting the sympathetic nervous system directly appears to be a logical therapeutic approach for the treatment of hypertension. However, Sympathetic nervous system is not immune against the viral infection susceptibility. Therefore, we have studied pathological issues driven by the Neuroinvasive viruses that give rise to the anatomical and physiological dysfunctions. That collectively results into the hypertension and other cardiac dysfunctions.

Angiotensin Converting Enzyme 2, Angiotensin-(1-7), and Receptor Mas Axis in the Kidney

In the past few years the understanding of the renin-angiotensin system (RAS) has improved, helping to better define the role of this system in physiological conditions and in human diseases. Besides Angiotensin (Ang) II, the biological importance of other Ang fragments was progressively evidenced. In this regard, Angiotensin- (Ang-) (1-7) was recognized as a biologically active product of the RAS cascade with a specific receptor, the G-protein-coupled receptor Mas, and that is mainly formed by the action of the angiotensin-converting enzyme (ACE) homolog enzyme, ACE2, which converts Ang II into Ang-(1-7). Taking into account the biological effects of these two mediators, Ang II and Ang-(1-7), the RAS can be envisioned as a dual function system in which the vasoconstrictor/proliferative or vasodilator/antiproliferative actions are primarily driven by the balance between Ang II and Ang-(1-7), respectively. In this paper, we will discuss our current understanding of the ACE2/Ang-(1-7)/Mas axis of the RAS in renal physiology and in the pathogenesis of primary hypertension and chronic kidney disease.

Angiotensin-(1-7)/Angiotensin-Converting Enzyme 2/Mas Receptor Axis and Related Mechanisms

Angiotensin-(1-7)/Angiotensin-Converting Enzyme 2/Mas Receptor Axis and Related Mechanisms