Sustained Elevation Of Blood Pressure Research Articles

Antidyslipidaemic evaluation of coagulin C and withacoagulin isolated from Withania coagulans (Stocks) dunal berries in hypertension induced secondary dyslipidemia in albino mice

Vascular diseases like hypertension has often been associated with dyslipidemia. Sustained elevated blood pressure for not less than four weeks develops gross irregularities inside arteriolar lumen. The pathological changes might be due to intimal arteriosclerotic thickening causing tapering of the structural narrowing along the arterioles. It might also be due to occurrence of irregular damage in the vascular structure from focal arteriolar constriction and lead to secondary dyslipidemia. The pharmacological intervention may lead to rectification and therapeutic benefit against dyslipidemia.The withanolides coagulin C and withacoagulin were isolated by flash chromatography from the extracts of Withania coagulans (Stocks) Dunal berries. The withanolides were characterized using 1H NMR and 13C NMR, UV and mass spectrometry and confirmed as coagulin C and withacoagulin. The oral toxicity of coagulin C and withacoagulin were investigated in albino mice followed by their antidyslipidemic activity with two dose levels i.e. 25 mg/kg and 50 mg/Kg p.o. This dyslipidemia was secondary to hypertension which was developed by DOCA salt model (25 mg/kg; s.c.+ 2% NaCl). Mice were administered dose of 10, 50 and 500 mg/kg coagulin C and withacoagulin orally for 28 days daily for sub-acute toxicity effect.Coagulin C and withacoagulin were found to be tolerated upto 2000 mg/kg p.o. during acute toxicity study in mice. Coagulin C and withacoagulin were claimed to possess No-Observed Adverse Effect Level (NOEL) at the dose of 500 mg/kg orally. The high dose (50 mg/Kg) withacoagulin has highly significant difference in total cholesterol, triglyceride, HDL, LDL and VLDL levels in comparison to disease control group along with highly significant difference in triglyceride and VLDL level compared to animals of vehicle control group. Coagulin C at both the low (25 mg/Kg) and high dose (50 mg/Kg) have highly significant difference in comparison to vehicle control, disease control and positive control in controlling total cholesterol, triglyceride, LDL and VLDL levels in the experimental animals indicating that coagulin C is not much as effective as withacoagulin in the normalization of altered lipid profile of the experimental animals.On the basis of spectroscopic analysis the isolated compounds from Withania coagulans (Stocks) Dunal berries were confirmed to be coagulin C and withacoagulin. Acute oral toxicity test in mice was found to have safe profile even at high dose for both the compounds. On development of secondary dyslipidemia due to DOCA salt induced hypertension in albino mice, both the isolated compounds showed different degree of correction in the altered lipid profile of the animals. Whereas withacoagulin has been found to have more significant and successful in controlling the altered lipid profile, coagulin C has only marginal effect. The docking studies also confirm the result and hence it can be suggested that withacoagulin is better than coagulin C in managing the alteration of lipid profile of the experimental mice.

The Role of Health Behaviors in the Prevention and Management of Hypertension in Pregnancy: Current Guidelines and Perspectives

Introduction and purpose Hypertensive disorders during pregnancy are related to a greater risk of both maternal, and fetal as well as neonatal morbidity and mortality. This literature review aims to synthesize the health-promoting behaviors in daily life like diet, body mass, exercises in the prevention and management of hypertension and possible complications. Gestational hypertension occurs after 20 weeks' pregnancy and usually resolves after 6 weeks' postpartum. Diagnosis of gestational hypertension appears at values >140/90 mmHg in pregnant women. It has to be confirmed in out-of-office BP measurements, and if it's not possible by two separate medical appointments. According to current European guidelines, pharmacological therapy should be introduced in pregnant women with sustained elevated blood pressure ≥ 150/95 mmHg and at values >140/90 mmHg in pregnant women with gestational hypertension. Summarizing the current understanding of risk factors in hypertensive disorders during pregnancy seeks to enhance implementing positive health behaviors in prevention. Materials and methods The following review of studies was based on articles obtained from the PubMed and Google Scholar databases. Key search terms included gestational hypertension, pre-eclampsia, diet, physical activity, pharmacological treatment, obesity, prevention. Conclusion The literature review highlights the importance of BP measurements, diet restrictions, exercises of a low to moderate-intensity, pharmacological treatment during pregnancy as key factors in prevention of gestational hypertension. Greater awareness of hypertension in pregnancy encourages optimism for comprehensive research in the future.

Evaluation of the inter-arm blood pressure difference in subjects with hypertension in Nnewi North Local Government Area, Anambra state

Hypertension is defined as a sustained elevated blood pressure with a systolic blood pressure (SBP) of 140mmHg or more and a diastolic blood pressure of 90mmHg or more. The evaluation of the inter-arm blood pressure difference in subjects with hypertension in Nnewi North Local Government Area, Anambra state was done via sampling techniques. The study population was obtained using convenience sampling method and comprised of male and female hypertensive patients aged 25 to 90 years, from the cardiology unit NAUTH Nnewi. Normotensive subjects of the same age range and gender were used as control. The sample size was determined to be 70 subjects using this formula: n= (z2pq)/d2). The result of the finding showed that there was a significant increase in the mean age when the control was compared to the hypertensive group, and no significant difference in their weight, height and BMI. Furthermore, the findings of this research also supported a significant increase in the left arterial systolic and diastolic blood pressure in the control compared to the hypertensive groups. Also, the mean right systolic and diastolic blood pressure showed a significant increase when the control was compared to the hypertensive group. The inter-arm systolic and diastolic blood pressure had no significant difference when control was compared to the hypertensive group.

Overview of the Evolution of Hypertension: From Ancient Chinese Emperors to Today.

Hypertension is one of the most commonly treated conditions in modern medical practice, but despite its long history, it was largely ignored until the midpoint of the 20th century. This article will review the origins of elevated blood pressure from when it was first appreciated in 2600 BC to its most recent emerging treatments. Awareness of sustained elevations in blood pressure goes back to the Chinese Yellow Emperor's Classic of Internal Medicine (2600 BC); even then, salt was appreciated as a contributor to elevated pressure. Early treatments included acupuncture, venesection, and bleeding by leeches. About 1000 years later, the association between the palpated pulse and the development of heart and brain diseases was described by Ebers Papyrus (1550 BC). But really, it has only been since well after World War II that hypertension has finally been appreciated as the cause of so much heart, stroke, and kidney disease. We review the development of effective treatments for hypertension while acknowledging that so many people with hypertension in need of treatment have unacceptably poor blood pressure control. We explore why, despite our considerable and growing knowledge of hypertension, it remains a significant public health problem globally.

Renal denervation restores biomechanics of carotid arteries in a rat model of hypertension

The prevalence of hypertension increases with aging and is associated with increased arterial stiffness. Resistant hypertension is presented when drug treatments fail to regulate a sustained increased blood pressure. Given that the mechanisms between the sympathetic nervous system and the kidney play an important role in blood regulation, renal denervation (RDN) has emerged as a therapeutic potential in resistant hypertension. In this study, we investigated the effects of RDN on the biomechanical response and microstructure of elastic arteries. Common carotid arteries (CCA) excised from 3-month, 8-month, and 8-month denervated rats were subjected to biaxial extension-inflation test. Our results showed that hypertension developed in the 8-month-old rats. The sustained elevated blood pressure resulted in arterial remodeling which was manifested as a significant stress increase in both axial and circumferential directions after 8 months. RDN had a favorable impact on CCAs with a restoration of stresses in values similar to control arteries at 3 months. After biomechanical testing, arteries were imaged under a multi-photon microscope to identify microstructural changes in extracellular matrix (ECM). Quantification of multi-photon images showed no significant alterations of the main ECM components, elastic and collagen fibers, indicating that arteries remained intact after RDN. Regardless of the experimental group, our microstructural analysis of the multi-photon images revealed that reorientation of the collagen fibers might be the main microstructural mechanism taking place during pressurization with their straightening happening during axial stretching.

Blood Pressure Regulation and Hypertension in Obstructive Sleep Apnea Syndrome: A Historical Perspective.

In obstructive sleep apnea syndrome (OSAS), an underlying disease of secondary hypertension, repeated episodes of asphyxia due to obstructive sleep apnea (OSA), followed by arousal, lead to various cardiovascular consequences. Using a canine model of OSAS, it was found that a single load of OSA caused an abrupt increase in blood pressure (BP) (Apnea Surge in seconds), while multiple OSA episodes occurring nightly for 1-3 months led to a sustained elevation of BP during both nighttime and daytime. Epidemiological studies on 24-hour ambulatory BP measurements revealed that some hypertensive patients experienced elevated BP in the early morning (Morning Surge), which could be intensified by OSAS. The resonance of Apnea Surge in seconds and Morning Surge increases the risk of organ damage, triggers the cardiovascular events, and adversely affects the prognosis of hypertensive patients with OSAS.For ameliorating these risks, OSA should be treated with positive airway pressure properly.

Synergizing the enhanced RIME with fuzzy K-nearest neighbor for diagnose of pulmonary hypertension

Pulmonary hypertension (PH) is an uncommon yet severe condition characterized by sustained elevation of blood pressure in the pulmonary arteries. The delaying treatment can result in disease progression, right ventricular failure, increased risk of complications, and even death. Early recognition and timely treatment are crucial in halting PH progression, improving cardiac function, and reducing complications. Within this study, we present a highly promising hybrid model, known as bERIME_FKNN, which constitutes a feature selection approach integrating the enhanced rime algorithm (ERIME) and fuzzy K-nearest neighbor (FKNN) technique. The ERIME introduces the triangular game search strategy, which augments the algorithm's capacity for global exploration by judiciously electing distinct search agents across the exploratory domain. This approach fosters both competitive rivalry and collaborative synergy among these agents. Moreover, an random follower search strategy is incorporated to bestow a novel trajectory upon the principal search agent, thereby enriching the spectrum of search directions. Initially, ERIME is meticulously compared to 11 state-of-the-art algorithms using the IEEE CEC2017 benchmark functions across diverse dimensionalities such as 10, 30, 50, and 100, ultimately validating its exceptional optimization capability within the model. Subsequently, employing the color moment and grayscale co-occurrence matrix methodologies, a total of 118 features are extracted from 63 PH patients' and 60 healthy individuals' images, alongside an analysis of 14,514 recordings obtained from these patients utilizing the developed bERIME_FKNN model. The outcomes manifest that the bERIME_FKNN model exhibits a conspicuous prowess in the realm of PH classification, attaining an accuracy and specificity exceeding 99%. This implies that the model serves as a valuable computer-aided tool, delivering an advanced warning system for diagnosis and prognosis evaluation of PH.

Corticotropin-releasing hormone neurons in the central nucleus of amygdala are required for chronic stress-induced hypertension.

Chronic stress is a well-known risk factor for the development of hypertension. However, the underlying mechanisms remain unclear. Corticotropin-releasing hormone (CRH) neurons in the central nucleus of the amygdala (CeA) are involved in the autonomic responses to chronic stress. Here, we determined the role of CeA-CRH neurons in chronic stress-induced hypertension. Borderline hypertensive rats (BHRs) and Wistar-Kyoto (WKY) rats were subjected to chronic unpredictable stress (CUS). Firing activity and M-currents of CeA-CRH neurons were assessed, and a CRH-Cre-directed chemogenetic approach was used to suppress CeA-CRH neurons. CUS induced a sustained elevation of arterial blood pressure (ABP) and heart rate (HR) in BHRs, while in WKY rats, CUS-induced increases in ABP and HR quickly returned to baseline levels after CUS ended. CeA-CRH neurons displayed significantly higher firing activities in CUS-treated BHRs than unstressed BHRs. Selectively suppressing CeA-CRH neurons by chemogenetic approach attenuated CUS-induced hypertension and decreased elevated sympathetic outflow in CUS-treated BHRs. Also, CUS significantly decreased protein and mRNA levels of Kv7.2 and Kv7.3 channels in the CeA of BHRs. M-currents in CeA-CRH neurons were significantly decreased in CUS-treated BHRs compared with unstressed BHRs. Blocking Kv7 channel with its blocker XE-991 increased the excitability of CeA-CRH neurons in unstressed BHRs but not in CUS-treated BHRs. Microinjection of XE-991 into the CeA increased sympathetic outflow and ABP in unstressed BHRs but not in CUS-treated BHRs. CeA-CRH neurons are required for chronic stress-induced sustained hypertension. The hyperactivity of CeA-CRH neurons may be due to impaired Kv7 channel activity, which represents a new mechanism involved in chronic stress-induced hypertension.

Attenuation of Myocardial Dysfunction in Hypertensive Cardiomyopathy Using Non-R-Wave-Synchronized Cardiac Shock Wave Therapy.

Cardiac shock wave therapy (CSWT) is a novel therapeutic procedure for patients with angina that is refractory to conventional therapy. We investigated the potential mechanism and therapeutic efficacy of non-R-wave-triggered CSWT to attenuate myocardial dysfunction in a large animal model of hypertensive cardiomyopathy. Sustained elevated blood pressure (BP) was induced in adult pigs using a combination of angiotensin-II and deoxycorticosterone acetate (DOCA). Two sessions of non-R-wave-triggered CSWT were performed at 11 and 16 weeks. At 10 weeks, systolic and diastolic blood pressure, LV posterior wall thickness and intraventricular septum thickness significantly increased in both the hypertension and CSWT groups. At 20 weeks, +dP/dt and end-systolic pressure-volume relationship (ESPVR) decreased significantly in the hypertension group but not the CSWT group, as compared with week 10. A significant improvement in end-diastolic pressure-volume relationship (EDPVR) was observed in the CSWT group. The CSWT group exhibited significantly increased microvascular density and vascular endothelial growth factor (VEGF) expression in the myocardium. Cytokine array demonstrated that the CSWT group had significantly reduced inflammation compared with the hypertension group. Our results demonstrate that non-R-wave-triggered CSWT is safe and can attenuate LV systolic and diastolic dysfunction via enhancement of myocardial neovascularization and anti-inflammatory effect in a large animal model of hypertensive cardiomyopathy.

Abstract 90: Meta-analysis Of Early Treatment Of Hypertension In Acute Ischemic Stroke And Functional Outcome

Introduction: Elevation in blood pressure (BP) in the early period following acute ischemic stroke (AIS) is frequent and likely due to a physiologic response to neurologic insult, damage to specific structures, and failure of cerebral autoregulation. It remains unclear whether early treatment of elevated BP after AIS influences clinical outcome in these patients. This meta-analysis aimed to investigate if treatment of sustained elevations in BP in the early period following AIS leads to a reduced risk of poor functional outcome. Method: Systematic review identifying randomized-controlled, double-blinded trials of AIS patients between 1994-2020 comparing those who receive anti-hypertensive medications within 72 hours of symptom-onset to those who do not receive medication. The primary outcome was poor functional outcome (defined by mRS > 2 at 90 days). Results were pooled using inverse variance random effects meta-analyses. Conclusions accounted for the magnitude of effect, precision, and risk of bias in the studies using the modified GRADE process of the American Academy of Neurology (AAN). Results: Ten randomized-controlled double-blinded studies totaling 15762 AIS patients met inclusion criteria. Baseline patient characteristics were without significant confounders. Mean symptom-onset to treatment time was 3-72 hours. The duration of treatment ranged from 3-90 days. Antihypertensive medications used included calcium-channel blockers, angiotensin receptor blockers, ACE-inhibitors, nitrates, and diuretics. Overall, poor functional outcome occurred in 32.4% of patients. There was no statistical difference in poor functional outcome in patients treated with antihypertensive medications within 72 hours of symptom-onset vs no treatment (OR=1.05, CI 95% 0.93-1.18). Conclusion: For the early period following AIS, treatment of sustained elevations in BP does not reduce the risk of mRS > 2 at 90 days. Confidence in the evidence is strong, anchored by selection of large randomized-controlled, double-blinded trials. Limitations include variable BP medications, initial stroke severities, and AIS mechanisms.

A Comparative Study of Tolerability of Losartan versus Atenolol in Essential Hypertension and Their Effect on Lipid Profile

Hypertension is a vascular disease entity that is a common problem occurring worldwide, characterized by sustained elevated blood pressure. Losartan and atenolol are two medications that are commonly used in hypertensive patients. However, the mechanism of tolerability their effect on lipid profile is not clearly described. Thus, the aims of this study were to study the tolerability of losartan with atenolol in patients with hypertension and the changes in lipid profile on treatment. This research was a prospective, open-label, parallel-group, comparative study conducted in the medicine out-patient department (OPD), where 100 patients aged 40-60 years with newly diagnosed mild and moderate hypertension. We classified patients randomly into two groups, losartan, and atenolol (50 patients of each). Patients were recruited for a period of 6 months and were called for follow-up visits at the third and sixth months. In this study mean age of the patients was 52.72 years. Our study observed that baseline systolic (P=0.704), as well as diastolic blood pressure (BP) (P=0.324), was comparable between both groups. Both systolic (P=0.125), as well as diastolic BP (P=0.108) at 6-months, was comparable between both groups. It was observed that mean total cholesterol levels were comparable between both groups at baseline (P=0.665). Moreover, adverse effects were observed more commonly in group atenolol, headache being the most common followed by dizziness and palpitation. Our study observed that both losartan and atenolol are equally effective in long- term reduction of blood pressure. Additionally, losartan also significantly improved lipid profile.

Kidney Function Decline in Young Adulthood and Subsequent 24-Hour Ambulatory Blood Pressure in Midlife: The CARDIA Study

Hypertension (HTN) and chronic kidney disease (CKD) are comorbid conditions. A decline in kidney function is associated with an increase in blood pressure (BP), and a sustained elevation in BP leads to the progression of kidney function decline.1 As CKD stage advances, the prevalence of HTN increases, and BP becomes more difficult to control.2

Genomics and Inflammation in Cardiovascular Disease.

Chronic cardiovascular diseases are associated with inflammatory responses within the blood vessels and end organs. The origin of this inflammation has not been certain, and neither is its relationship to disease clear. There is a need to determine whether this association is causal or coincidental to the processes leading to cardiovascular disease. These processes are themselves complex: many cardiovascular diseases arise in conjunction with the presence of sustained elevation of blood pressure. Inflammatory processes have been linked to hypertension, and causality has been suggested. Evidence of causality poses the difficult challenge of linking the integrated and multifaceted biology of blood pressure regulation with vascular function and complex elements of immune system function. These include both, innate and adaptive immunity, as well as interactions between the host immune system and the omnipresent microorganisms that are encountered in the environment and that colonize and exist in commensal relationship with the host. Progress has been made in this task and has drawn on experimental approaches in animals, much of which have focused on hypertension occurring with prolonged infusion of angiotensin II. These laboratory studies are complemented by studies that seek to inform disease mechanism by examining the genomic basis of heritable disease susceptibility in human populations. In this realm too, evidence has emerged that implicates genetic variation affecting immunity in disease pathogenesis. In this article, we survey the genetic and genomic evidence linking high blood pressure and its end-organ injuries to immune system function and examine evidence that genomic factors can influence disease risk. © 2021 American Physiological Society. Compr Physiol 11:1-22, 2021.

Sustained Elevated Blood Pressure Accelerates Atherosclerosis Development in a Preclinical Model of Disease.

The continuous relationship between blood pressure (BP) and cardiovascular events makes the distinction between elevated BP and hypertension based on arbitrary cut-off values for BP. Even mild BP elevations manifesting as high-normal BP have been associated with cardiovascular risk. We hypothesize that persistent elevated BP increases atherosclerotic plaque development. To evaluate this causal link, we developed a new mouse model of elevated BP based on adeno-associated virus (AAV) gene transfer. We constructed AAV vectors to support transfer of the hRenin and hAngiotensinogen genes. A single injection of AAV-Ren/Ang (1011 total viral particles) induced sustained systolic BP increase (130 ± 20 mmHg, vs. 110 ± 15 mmHg in controls; p = 0.05). In ApoE−/− mice, AAV-induced mild BP elevation caused larger atherosclerotic lesions evaluated by histology (10-fold increase vs. normotensive controls). In this preclinical model, atheroma plaques development was attenuated by BP control with a calcium channel blocker, indicating that a small increase in BP within a physiological range has a substantial impact on plaque development in a preclinical model of atherosclerosis. These data support that non-optimal BP represents a risk for atherosclerosis development. Earlier intervention in elevated BP may prevent or delay morbidity and mortality associated with atherosclerosis.

Activation of the intestinal tissue renin-angiotensin system by transient sodium loading in salt-sensitive rats.

Background:The renal tissue renin-angiotensin system is known to be activated by salt loading in salt-sensitive rats; however, the response in other organs remains unclear.Method:Spontaneously hypertensive rats were subjected to normal tap water or transient high-salt-concentration water from 6 to 14 weeks of age and were thereafter given normal tap water. From 18 to 20 weeks of age, rats given water with a high salt concentration were treated with an angiotensin II type 1 receptor blocker, valsartan.Results:Sustained blood pressure elevation by transient salt loading coincided with a persistent decrease in the fecal sodium content and sustained excess of the circulating volume in spontaneously hypertensive rats. Administration of valsartan sustainably reduced the blood pressure and normalized the fecal sodium levels. Notably, transient salt loading persistently induced the intestinal tissue renin-angiotensin system and enhanced sodium transporter expression exclusively in the small intestine of salt-sensitive rats, suggesting the potential connection of intestinal sodium absorption to salt sensitivity.Conclusion:These results reveal the previously unappreciated contribution of the intestinal tissue renin-angiotensin system to sodium homeostasis and blood pressure regulation in the pathophysiology of salt-sensitive hypertension.

Twenty-Four-Hour Blood Pressure Variability Is Associated With Lower Cognitive Performance in Young Women With a Recent History of Preeclampsia.

Women with a history of preeclampsia (hxPE) exhibit sustained arterial stiffness and elevated blood pressure postpartum. Aortic stiffness and 24-hour blood pressure variability (BPV) are associated with age-related cognitive decline. Although hxPE is related to altered cognitive function, the association between aortic stiffness and BPV with cognitive performance in young women with hxPE has not been investigated. The objectives of this study were to (i) test whether cognitive performance is lower in young women with hxPE and (ii) determine whether aortic stiffness and BPV are associated with cognitive performance independent of 24-hour average blood pressure. Women with hxPE (N = 23) and healthy pregnancy controls (N = 38) were enrolled 1-3 years postpartum. Cognitive performance was assessed in domains of memory, processing speed, and executive function. Twenty-four-hour ambulatory blood pressure monitoring and carotid-femoral pulse wave velocity (cfPWV) were used to measure BPV and aortic stiffness, respectively. Women with hxPE had slower processing speed (-0.56 ± 0.17 vs. 0.34 ± 0.11 Z-score, P < 0.001) and lower executive function (-0.43 ± 0.14 vs. 0.31 ± 0.10 Z-score, P = 0.004) compared with controls independent of education, whereas memory did not differ. BPV and cfPWV (adjusted for blood pressure) did not differ between women with hxPE and controls. Greater diastolic BPV was associated with lower executive function independent of 24-hour average blood pressure and education in women with hxPE (r = -0.48, P = 0.03) but not controls (r = 0.15, P = 0.38). Select cognitive functions are reduced postpartum in young women with a recent hxPE and linked with elevated 24-hour diastolic BPV.

Aldosterone contributes to hypertension in male mice inducibly overexpressing human endothelin-1 in endothelium

Mechanisms of blood pressure (BP) regulation by endothelin (ET)-1 produced by endothelial cells are complex and remain unclear. Long-term exposure to human ET-1 (hET-1) in mice inducibly overexpressing hET-1 in the endothelium (ieET-1) caused sustained BP elevation. ET-1 has been shown to stimulate the release of aldosterone. Whether aldosterone plays a role in hET-1 overexpression-induced BP elevation and vessel injury is unknown. Nine- to 12-week-old male ieET-1 mice and control mice expressing a tamoxifen-inducible Cre recombinase (CreERT2) in the endothelial cells (ieCre) were treated with tamoxifen for 5 days and studied 3 months later. Endothelial hET-1 overexpression increased plasma aldosterone levels, which was reversed by 2-week treatment with atrasentan, an endothelin type A receptors blocker. Aldosterone synthase and cryptochrome 2 adrenal cortex mRNA expression was decreased in ieET-1 mice. Two-week treatment with eplerenone, a mineralocorticoid receptor antagonist, reduced systolic BP by 10 mmHg in ieET-1 mice during rest time. Saline challenge-induced sodium excretion and renal cortex thiazide-sensitive sodium-chloride cotransporter mRNA expression were decreased in ieET-1 mice. The sensitivity of mesenteric arteries to contraction by norepinephrine was increased in ieET-1 mice, and was abrogated by eplerenone treatment, whereas sensitivity of endothelium-independent relaxation responses to sodium nitroprusside was enhanced. Resistance artery remodeling was reduced in eplerenone-treated ieET-1 vs. ieET-1 and ieCre mice. These results demonstrate that aldosterone contributes to BP elevation and vascular norepinephrine sensitivity and remodeling caused by hET-1 overexpression in endothelium in mice.

Activation of Corticotropin‐Releasing Hormone Neurons in the Central Nucleus of Amygdala is required for Chronic Stress‐Induced Hypertension

Background Chronic stress is a well-known risk factor for the etiology of hypertension. However, the underlying neural mechanisms remain largely unknown. Corticotropin-releasing hormone (CRH) neuroendocrine cells in central nucleus of the amygdala (CeA) are critical in mediating autonomic response to chronic stress. Therefore, we determined the role of CeA-CRH neurons in hypertension induced by chronic stress. Methods Broadline hypertensive rats (BHRs) were subjected to chronic unpredictable stress (CUS). Identified CeA-CRH neuron firing activity and M-currents were recorded by whole-cell patch-clamp technique in brain slice preparation. A CRH-Cre-directed chemogenetic approach was used to suppress CeA-CRH neurons. Kv7 channel protein and mRNA level were determined by western-blot and quantitative RT-PCR methods, respectively. Results CUS treatment induced a sustained elevation of blood pressure in BHRs and a significant increase in c-Fos expression CeA-CRH neurons. Identified CeA-CRH neurons displayed significantly higher spontaneous firing activities in BHRs subjected to CUS than in unstressed BHRs. Specifically suppressing CeA-CRH neurons activity by using CRH-Cre-directed chemogenetic approach restrained CUS-induced sustained hypertension in BHRs. Both mRNA and protein levels of Kv7.2 and Kv7.3 channels were decreased in CeA of BHRs subjected to CUS. M-currents recorded from CeA-CRH neurons were significantly decreased in CUS BHRs compared with unstressed BHRs. Blocking Kv7 channel with its specific antagonist increased excitability of CeA-CRH neurons in unstressed BHRs whereas did not alter their excitability in BHRs subjected to CUS. Conclusions These data suggest that CeA-CRH neurons are required for the development of chronic stress-induced hypertension. The hyperactivity of CeA-CRH neurons is due to impaired Kv7 channel activity induced by chronic stress. These findings revealed a novel mechanism involved in chronic stress-induced hypertension.

HEMODYNAMIC EVALUATION OF TREATED HYPERTENSIVE PATIENTS WITH IMPEDANCE CARDIOGRAPHY: RESULTS OF IMPEDDANS STUDY

Objective: The prevalence of arterial hypertension (AHT) in Portuguese adult population is higher than 40%. Historically defined by sustained elevation of blood pressure (BP), AHT results from hemodynamic changes characterized by cardiac output, systemic vascular resistance and/or arterial compliance abnormalities, with significant implications for diagnosis, risk stratification and treatment. Impedance cardiography (ICG) is a noninvasive method for hemodynamic profile evaluation. It allows to access risk and optimize therapy. In this study we analyzed the resistant hypertensive patients with controlled blood pressure values in order to evaluate and characterize their hemodynamic profile by ICG. Design and method: Resistant hypertensive patients without heart failure, ischemic heart disease, valvular heart disease or dysrhythmia were prospectively selected. After ICG were classified as: vasoconstrictor (systemic vascular resistance (SVR) &gt; 2500dyn.s.cm-5.m2), hyperdynamic (cardiac index (CI) &gt; 4.2l/min/m2 and/or heart rate (HR) &gt; 80 cycles/min), hypervolemic (thoracic fluid (TFC) &gt; 341/kOhm) or balanced (hemodynamic parameters below the established limit values). All patients underwent transthoracic echocardiography to exclude major changes. In this sub-analysis of patients from the IMPEDDANS study we included only those who, according to international recommendations, had office and outpatient blood pressure values within the therapeutic goals. Results: From 178 initial patients, 52 were included, 57.7% male, with 63 ± 9 years old, under 4 ± 1 antihypertensive agents. The mean hemodynamic values were: systolic blood pressure (BP) 125 ± 12, diastolic BP 75 ± 6, HR 69 ± 11, SVR 2756 ± 527, CI 2.8 ± 0.5, TFC 32 ± 4. According to the hemodynamic profile 63.7% appear to be vasoconstrictors, 13.5% hyperdynamic, 28.7% hypervolemic and 22.9% balanced. Conclusions: These results suggest that, despite polymedicated and with arterial pressure within the recommended values, the majority of patients were not hemodynamically stabilized, confirming that BP is an hemodynamic variable supported by several processes, tendentially redundant, in which inhibition of one element tends to favor the activation of another. ICG is, therefore, an useful method in the evaluation of hypertensive individuals, capable of contributing to adequate therapeutic optimization.

Current challenges for hypertension management: From better hypertension diagnosis to improved patients' adherence and blood pressure control

Hypertension control still remains a largely unmet challenge for public health systems. Despite the progress in blood pressure (BP) measurement techniques, and the availability of effective and safe antihypertensive drugs, a large number of hypertensive patients are not properly identified, and a significant proportion of those who receive antihypertensive treatment fail to achieve satisfactory control of their BP levels. It is thus not surprising that hypertension is still a major contributor to disease burden and disability worlwide, even in developed countries. This paper will address current challenges in hypertension management and potential strategies for an improvement in this field. In its first part relevant issues related to hypertension diagnosis will be addressed, in particular how to improve identification of sustained BP elevation and specific BP phenotypes such as white coat and masked hypertension trough the combined use of office and out-of-office BP monitoring techniques. In its second part focus will be on how to improve achievement of hypertension control in treated patients by optimization and simplification of medication regimens, including more efficient selection and titration of antihypertensive drugs and their combinations, aimed at achieving a more consistent 24hBP control; and by favoring a more active patients' and physicians' involvement in hypertension management also through BP telemonitoring and mobile health technologies.