Adıyaman Üniversitesi Mühendislik Bilimleri Dergisi
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Open Access journal
ISSN (Print) 2149-0309
Published by Adıyaman Üniversitesi [2 journals]
- The Gut Microbiome, Energy Homeostasis, and Implications for Hypertension
Abstract: Purpose of Review The influence of gut bacteria upon host physiology is increasingly recognized, but mechanistic links are lacking. Diseases of energetic imbalance such as obesity and diabetes represent major risk factors for cardiovascular diseases such as hypertension. Thus, here, we review current mechanistic contributions of the gut microbiota to host energetics. Recent Findings Gut bacteria generate a multitude of small molecules which can signal to host tissues within and beyond the gastrointestinal tract to influence host physiology, and gut bacteria can also influence host digestive efficiency by altering the bioavailability of polysaccharides, yet the quantitative energetic effects of these processes remain unclear. Recently, our team has demonstrated that gut bacteria constitute a major anaerobic thermogenic biomass, which can quantitatively account for obesity. Summary Quantitative understanding of the mechanisms by which gut bacteria influence energy homeostasis may ultimately inform the relationship between gut bacteria and cardiovascular dysfunction.
- Microbial Short-Chain Fatty Acids and Blood Pressure Regulation
Abstract: Purpose of Review Microbial short-chain fatty acids (SCFAs) are byproducts of microbial metabolism which can be absorbed into the bloodstream of the host, where they exert effects on host physiology. SCFAs have been known to influence several aspects of host physiology, including the regulation of blood pressure. In this review, we will consider recent studies linking SCFAs to blood pressure regulation. Recent Findings Several recent studies have found that changes in blood pressure often coordinate with expected changes in SCFAS. Efforts are now well underway to dissect and better understand this potential connection. One way that SCFAs can influence host cells is by interacting with host GPCRs, including Gpr41 and Olfr78, among others. Intriguingly, mice null for Olfr78 are hypotensive, whereas mice null for Gpr41 are hypertensive, implying that these pathways may be physiologically important links between SCFAs and host blood pressure control. Summary In sum, these studies demonstrate that there does indeed appear to be a link between SCFAs and blood pressure, which likely involves host GPCRs, at least in part; however, the details and intricacies of these interactions are not yet fully understood and will greatly benefit from further studies.
- Antihypertensive Effects of Probiotics
Abstract: Purpose of Review The present review focuses in the hypertension-associated changes in the microbiota and the current insights regarding the impact of probiotics on blood pressure in animal models and in human hypertensive patients. Recent Findings Gut dysbiosis in hypertension is characterized by (i) the gut microbioma that is less diverse and less rich with an increased Firmicutes/Bacteroidetes ratio and (ii) a decrease in acetate- and butyrate-producing bacteria and an increase in lactate-producing bacterial populations. The meta-analysis of the human studies supports that supplementation with probiotics reduces blood pressure. The mechanism of this antihypertensive effect of probiotics and its protective effect on endothelial function has not been fully elucidated. Summary Further investigations are needed to clarify if the effects of probiotic bacteria result from the changes in the gut microbiota and its metabolic by-products; the restoration of the gut barrier function; and the effects on endotoxemia, inflammation, and renal sympathetic nerve activity.
- Defining the Relationship Between Hypertension, Cognitive Decline, and
Dementia: a Review
Abstract: Hypertension is a highly prevalent condition which has been established as a risk factor for cardiovascular and cerebrovascular disease. Although the understanding of the relationship between cardiocirculatory dysfunction and brain health has improved significantly over the last several decades, it is still unclear whether hypertension constitutes a potentially treatable risk factor for cognitive decline and dementia. While it is clear that hypertension can affect brain structure and function, recent findings suggest that the associations between blood pressure and brain health are complex and, in many cases, dependent on factors such as age, hypertension chronicity, and antihypertensive medication use. Whereas large epidemiological studies have demonstrated a consistent association between high midlife BP and late-life cognitive decline and incident dementia, associations between late-life blood pressure and cognition have been less consistent. Recent evidence suggests that hypertension may promote alterations in brain structure and function through a process of cerebral vessel remodeling, which can lead to disruptions in cerebral autoregulation, reductions in cerebral perfusion, and limit the brain’s ability to clear potentially harmful proteins such as β-amyloid. The purpose of the current review is to synthesize recent findings from epidemiological, neuroimaging, physiological, genetic, and translational research to provide an overview of what is currently known about the association between blood pressure and cognitive function across the lifespan. In doing so, the current review also discusses the results of recent randomized controlled trials of antihypertensive therapy to reduce cognitive decline, highlights several methodological limitations, and provides recommendations for future clinical trial design.
- A Review of the Genetics of Hypertension with a Focus on Gene-Environment
Abstract: Purpose of Review Here, we discuss the interpretation and modeling of gene-environment interactions in hypertension-related phenotypes, with a focus on the necessary assumptions and possible challenges. Recent Findings Recently, small cohort studies have discovered several novel genetic variants associated with hypertension-related phenotypes through modeling gene-environment interactions. Several consortia-based meta-analytic efforts have uncovered many novel genetic variants in hypertension without modeling interaction terms, giving promise to future meta-analytic efforts that incorporate gene-environment interactions. Summary Heritability studies and genome-wide association studies have established that hypertension, a prevalent cardiovascular disease, has a genetic component that may be modulated by the environment (such as lifestyle factors). This review includes a discussion of known genetic associations for hypertension/blood pressure, including those resulting from the incorporation of gene-environmental interaction modeling.
- Differential Metabolic Effects of Beta-Blockers: an Updated Systematic
Review of Nebivolol
Abstract: Blood pressure management in hypertensive patients with metabolic abnormalities is challenging, since many of the antihypertensive drugs adversely affect metabolism. Besides effective control of blood pressure in patients with hypertension, third-generation beta-blockers such as nebivolol offer additional benefits for central hemodynamics and neutral or beneficial effects on metabolism. Emerging clinical data suggest that nebivolol also has similar effects on metabolism in obese hypertensive and hypertensive diabetic patients. The present article will provide a systematic analysis of the pathophysiological links among hypertension, insulin resistance, and metabolic syndrome. We will also summarize the available clinical evidence regarding the metabolic effects of beta-blockers in hypertensive patients, with an emphasis on nebivolol. Nebivolol exerts neutral or beneficial effects on insulin sensitivity and lipid metabolism in hypertensive patients, owing to its nitric oxide-mediated vasodilatory and antioxidative properties. Thus, nebivolol could be a favorable therapeutic option for the treatment of hypertension in patients with impaired glucose and lipid metabolism.
- Pre-eclampsia: the Potential of GSNO Reductase Inhibitors
Abstract: Purpose of Review Pre-eclampsia remains a leading worldwide cause of maternal death and of perinatal morbidity. There remains no definitive treatment except delivery of the fetus. Recent Findings Recent insights into the cardiovascular changes that are evident prior to, during, and persist after pre-eclampsia have improved understanding of the underlying pathophysiology—disruption of normal endothelial function and decreased nitric oxide bioavailability. S-nitrosoglutathione (GSNO) is an endogenous S-nitrosothiol that acts as a NO pool and, by replenishing or preventing the breakdown of GSNO, endothelial dysfunction can be ameliorated. GSNO reductase inhibitors are a novel class of drug that can increase NO bioavailability. Summary GSNO reductase inhibitors have demonstrated improvement of endothelial dysfunction in animal models, and in vivo human studies have shown them to be well tolerated. GSNOR inhibitors offer a potentially promising option for the management of pre-eclampsia.
- Blood Pressure and the Renal Actions of AT 2 Receptors
Abstract: Angiotensin type-2 receptors (AT2Rs) in the renal proximal tubule inhibit sodium (Na+) reabsorption by inducing renal cyclic GMP formation and internalizing and inhibiting major Na+ transporters Na+-H+ exchanger-3 (NHE-3) and Na+/K+ATPase (NKA). Instead of angiotensin II (Ang II), angiotensin III (Ang III) is the predominant endogenous agonist for this response. Exogenous non-peptide AT2R agonist Compound-21 induces natriuresis and lowers blood pressure (BP) in normal and Ang II-infused hypertensive rodents. Spontaneously hypertensive rats (SHR; both pre-hypertensive and hypertensive) have defective natriuretic responses to Ang III, suggesting a defect in AT2R-mediated natriuresis in SHR that leads to hypertension. The mechanisms of deficient AT2R-mediated natriuresis in SHR are unknown but could involve either pre-receptor or receptor/post-receptor defects.
- Method of Blood Pressure Measurement, Interpretation of SPRINT, and the
- Pathophysiology and Potential Non-Pharmacologic Treatments of Obesity or
Kidney Disease Associated Refractory Hypertension
Abstract: Purpose of Review The review assesses the role of non-pharmacologic therapy for obesity and chronic kidney disease (CKD) associated refractory hypertension (rf HTN). Recent Findings Hypertensive patients with markedly heightened sympathetic nervous system (SNS) activity are prone to develop refractory hypertension (rfHTN). Patients with obesity and chronic kidney disease (CKD)-associated HTN have particularly heightened SNS activity and are at high risk of rfHTN. The role of bariatric surgery is increasingly recognized in treatment of obesity. Summary Current evidence advocates for a greater role of bariatric surgery in the management of obesity-associated HTN. In contrast, renal denervation does not appear have a role in the management of obesity or CKD-associated HTN. The role of baroreflex activation as adjunctive anti-hypertensive therapy remains to be defined.
- Ambiguities in the Guidelines for the Management of Arterial Hypertension:
Indian Perspective with a Call for Global Harmonization
Abstract: Many medical professional societies have formulated guidelines to treat hypertension, but there existed differences with respect to diagnosis, blood pressure (BP) targets, pharmacotherapy of hypertension, and grades of evidence. A MEDLINE search for hypertension guidelines was performed to compare Indian guidelines for hypertension (IGH) with these guidelines. A majority of the guidelines had consensus on the cutoff value (140/90 mmHg, recorded twice) to diagnose hypertension. The Joint National Committee 8 (JNC 8), IGH, Japanese Society of hypertension (JSH), Canadian Hypertension Education Program (CHEP), and American Society of Hypertension/International Society of Hypertension (ASH/ISH) guidelines provide a higher BP target for the elderly hypertensive populations, while the National Institute for Health and Care Excellence (NICE) and European Society of Hypertension (ESH) guidelines provided a lower BP target for the elderly patients. However, a meta-analysis showed benefits of having a systolic BP target of <130 mmHg for all patients. Treatment of hypertension according to JNC 8, NICE, and ASH/ISH guidelines varies among the black and the non-black population which recommended thiazide or calcium channel blockers for the black population. There is no special mention of pharmacotherapy or BP targets for the South Asian population in various guidelines including IGH despite evidence of higher risk of hypertension-associated complications in this population. It is suggested that all the available guidelines should be harmonized with highest level of evidence available to minimize ambiguities associated with management of hypertension.
- Plasticity of Renin Cells in the Kidney Vasculature
Abstract: During development, renin cells are precursors for arteriolar smooth muscle, mesangial cells, and interstitial pericytes. Those seemingly differentiated descendants retain the memory to re-express renin when there is a threat to homeostasis. Understanding how such molecular memory is constructed and regulated would be crucial to comprehend cell identity which is, in turn, intimately linked to homeostasis.
- Preeclampsia: a Cardiorenal Syndrome in Pregnancy
- Effects of Intrauterine Growth Restriction and Female Sex on Future Blood
Pressure and Cardiovascular Disease
Abstract: Purpose of the Review It is well-established that the age-related increase in blood pressure is augmented after menopause. Yet, the prevalence of hypertension is enhanced in low birth weight women relative to normal birth weight counterparts by 60 years of age suggesting that adverse influences during fetal life heighten cardiovascular risk in later life. Recent Findings A changing hormonal milieu may contribute to increased cardiovascular risk that occurs after the menopausal transition. Low birth weight is associated with early age at menopause. A recent study indicates that a shift towards testosterone excess following early reproductive senescence may contribute to the etiology of age-dependent increases in blood pressure in a rodent model of low birth weight. Summary This review will highlight current findings related to postmenopausal hypertension and discuss potential mechanisms that may contribute to the enhanced cardiovascular risk that develops with age in low birth weight women.
- Novel Cardiac Intracrine Mechanisms Based on Ang-(1-12)/Chymase Axis
Require a Revision of Therapeutic Approaches in Human Heart Disease
Abstract: Purpose of the Review Drugs targeting the renin-angiotensin system (RAS), namely angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers, are the most commonly prescribed drugs for patients with or at risk for cardiovascular events. However, new treatment strategies aimed at mitigating the rise of the heart failure pandemic are warranted because clinical trials show that RAS blockers have limited benefits in halting disease progression. The main goal of this review is to put forward the concept of an intracrine RAS signaling through the novel angiotensin-(1-12)/chymase axis as the main source of deleterious angiotensin II (Ang II) in cardiac maladaptive remodeling leading to heart failure (HF). Recent Findings Expanding traditional knowledge, Ang II can be produced in tissues independently from the circulatory renin-angiotensin system. In the heart, angiotensin-(1-12) [Ang-(1-12)], a recently discovered derivative of angiotensinogen, is a precursor of Ang II, and chymase rather than ACE is the main enzyme contributing to the direct production of Ang II from Ang-(1-12). The Ang-(1-12)/chymase axis is an independent intracrine pathway accounting for the trophic, contractile, and pro-arrhythmic Ang II actions in the human heart. Ang-(1-12) expression and chymase activity have been found elevated in the left atrial appendage of heart disease subjects, suggesting a pivotal role of this axis in the progression of HF. Summary Recent meta-analysis of large clinical trials on the use of ACE inhibitors and angiotensin receptor blockers in cardiovascular disease has demonstrated an imbalance between patients that significantly benefit from these therapeutic agents and those that remain at risk for heart disease progression. Looking to find an explanation, detailed investigation on the RAS has unveiled a previously unrecognized complexity of substrates and enzymes in tissues ultimately associated with the production of Ang II that may explain the shortcomings of ACE inhibition and angiotensin receptor blockade. Discovery of the Ang-(1-12)/chymase axis in human hearts, capable of producing Ang II independently from the circulatory RAS, has led to the notion that a tissue-delimited RAS signaling in an intracrine fashion may account for the deleterious effects of Ang II in the heart, contributing to the transition from maladaptive cardiac remodeling to heart failure. Targeting intracellular RAS signaling may improve current therapies aimed at reducing the burden of heart failure.
- Role of Mitochondrial Dysfunction in Hypertension and Obesity
Abstract: Mitochondria are essential for the maintenance of normal physiological function of tissue cells. Mitochondria are subject to dynamic processes in order to establish a control system related to survival or cell death and adaptation to changes in the metabolic environment of cells. Mitochondrial dynamics includes fusion and fission processes, biogenesis, and mitophagy. Modifications of mitochondrial dynamics in organs involved in energy metabolism such as the pancreas, liver, skeletal muscle, and white adipose tissue could be of relevance for the development of insulin resistance, obesity, and type 2 diabetes. Mitochondrial dynamics and the factors involved in its regulation are also critical for neuronal development, survival, and function. Modifications in mitochondrial dynamics in either agouti-related peptide (AgRP) or pro-opiomelanocortin (POMC), circuits which regulates feeding behavior, are related to changes of food intake, energy balance, and obesity development. Activation of the sympathetic nervous system has been considered as a crucial point in the pathogenesis of hypertension among obese individuals and it also plays a key role in cardiac remodeling. Hypertension-related cardiac hypertrophy is associated with changes in metabolic substrate utilization, dysfunction of the electron transport chain, and ATP synthesis. Alterations in both mitochondrial dynamics and ROS production have been associated with endothelial dysfunction, development of hypertension, and cardiac hypertrophy. Finally, it might be postulated that alterations of mitochondrial dynamics in white adipose tissue could contribute to the development and maintenance of hypertension in obesity situations through leptin overproduction. Leptin, together with insulin, will induce activation of sympathetic nervous system with consequences at renal, vascular, and cardiac levels, driving to sodium retention, hypertension, and left ventricular hypertrophy. Moreover, both leptin and insulin will induce mitochondrial alterations into arcuate nucleus leading to signals driving to increased food intake and reduced energy expenditure. This, in turn would perpetuate white adipose tissue excess and its well-known metabolic and cardiovascular consequences.
- Current Perspectives on Systemic Hypertension in Heart Failure with
Preserved Ejection Fraction
Abstract: Heart failure with preserved ejection fraction (HFpEF) is a prevalent but incompletely understood syndrome. Traditional models of HFpEF pathophysiology revolve around systemic HTN and other causes of increased left ventricular afterload leading to left ventricular hypertrophy (LVH) and diastolic dysfunction. However, emerging models attribute the development of HFpEF to systemic proinflammatory changes secondary to common comorbidities which include HTN. Alterations in passive ventricular stiffness, ventricular-arterial coupling, peripheral microvascular function, systolic reserve, and chronotropic response occur. As a result, HFpEF is heterogeneous in nature, making it difficult to prescribe uniform therapies to all patients. Nonetheless, treating systemic HTN remains a cornerstone of HFpEF management. Antihypertensive therapies have been linked to LVH regression and improvement in diastolic dysfunction. However, to date, no therapies have definitive mortality benefit in HFpEF. Non-pharmacologic management for HTN, including dietary modification, exercise, and treating sleep disordered breathing, may provide some morbidity benefit in the HFpEF population. Future research is need to identify effective treatments, perhaps in more specific subgroups, and focus may need to shift from reducing mortality to improving exercise capacity and symptoms. Tailoring antihypertensive therapies to specific phenotypes of HFpEF may be an important component of this strategy.
- Selenium, Vanadium, and Chromium as Micronutrients to Improve Metabolic
Abstract: Trace metals play an important role in the proper functioning of carbohydrate and lipid metabolism. Some of the trace metals are thus essential for maintaining homeostasis, while deficiency of these trace metals can cause disorders with metabolic and physiological imbalances. This article concentrates on three trace metals (selenium, vanadium, and chromium) that may play crucial roles in controlling blood glucose concentrations possibly through their insulin-mimetic effects. For these trace metals, the level of evidence available for their health effects as supplements is weak. Thus, their potential is not fully exploited for the target of metabolic syndrome, a constellation that increases the risk for cardiovascular disease and type 2 diabetes. Given that the prevalence of metabolic syndrome is increasing throughout the world, a simpler option of interventions with food supplemented with well-studied trace metals could serve as an answer to this problem. The oxidation state and coordination chemistry play crucial roles in defining the responses to these trace metals, so further research is warranted to understand fully their metabolic and cardiovascular effects in human metabolic syndrome.
- Multidisciplinary Approach in the Treatment of Resistant Hypertension
Abstract: With its high prevalence and the eminent number of undetected or poorly controlled patients, the management of arterial hypertension is still a challenging task. Uncontrolled blood pressure is the major adjustable risk factor for cardiovascular end organ damage for coronary heart disease, heart failure, stroke, and renal disease. Patients with resistant hypertension often need a multidisciplinary approach in order to control their blood pressure sustainably. In cooperation with hypertension specialists, the underlying cause for therapy resistance should be evaluated. Pseudohypertension, white coat hypertension, and non-adherence need to be addressed. The medication can often be optimized and simplified. Reducing the number of pills per day can enhance the drug-adherence remarkably. The multidisciplinary evaluation of secondary causes of hypertension includes an endocrinological work-up, ruling out relevant sleeping disorders, and renal diagnostics. If there are no causative treatments possible and pharmacological and non-pharmacological measurements are not sufficient to control the blood pressure, one has to consider multidisciplinary approaches bringing nurses, pharmacists, dieticians, physiotherapists, social workers, psychologists, and community health workers onboard. Utilizing various strategies might improve medication management, patient follow-up, adherence, and self-management. Interventional therapy such as renal renervation, baroreflex activation therapy, or carotid body modulation is the final option that can be discussed with interventional active colleagues. However, large randomized controlled trials proving a benefit of these interventional therapies are still missing. The use of these still experimental approaches should be restricted to randomized controlled trials accordingly.
- Hot Topic: Global Burden of Treating Hypertension—What is the Role of
the Emergency Department?
Abstract: Hypertension (HTN) is the most common modifiable risk factor for cardiovascular disease (CVD) morbidity and mortality worldwide. Lower- and middle-income countries (LMICs) are projected to bear the vast majority of this disease burden, but local and regional health care delivery systems in these countries are ill equipped to meet this need. Emergency care is receiving increased recognition as a crucial component of public and community health. The rapid evolution of emergency care in LMICs provides a unique opportunity to develop innovative strategies, incorporating existing strengths of emergency departments, to address this paradigm shift in the disease burden associated with HTN on a global scale.