Potential Therapeutic Use of Neurosteroids for Hypertension

The sympathetic nervous system (SNS) contribution to long-term setting of blood pressure (BP) and hence hypertension has been a continuing controversy over many decades. However, the contribution of increased sympathetic vasomotor tone to the heart, kidney, and blood vessels has been suggested as a major influence on the development of high BP which affects 30–40% of the population. This is relevant to hypertension associated with chronic stress, being overweight or obese as well to chronic kidney disease. Treatments that have attempted to block the peripheral aspects of the SNS contribution have included surgery to cut the sympathetic nerves as well as agents to block α- and β-adrenoceptors. Other treatments, such as centrally acting drugs like clonidine, rilmenidine, or moxonidine, activate receptors within the ventrolateral medulla to reduce the vasomotor tone overall but have side effects that limit their use. None of these treatments target the cause of the enhanced sympathetic tone. Recently we have identified an antihypertensive action of the neurosteroid allopregnanolone in a mouse model of neurogenic hypertension. Allopregnanolone is known to facilitate high-affinity extra-synaptic γ-aminobutyric acid A receptors (GABAAR) through allosteric modulation and transcriptional upregulation. The antihypertensive effect was specific for increased expression of δ subunits in the amygdala and hypothalamus. This focused review examines the possibili...
Source: Frontiers in Physiology - Category: Physiology Source Type: research

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Conclusion There is a long way ahead regarding the role of gut microbiota in the pathogenesis and as an adjunctive treatment of hypertension. Treatment of dysbiosis could be a useful therapeutic approach to add to traditional antihypertensive therapy. Manipulating gut microbiota using prebiotics and probiotics might prove a valuable tool to traditional antihypertensives.
Source: Journal of Cardiovascular Medicine - Category: Cardiology Tags: Review Source Type: research
Hui-Min Liu1,2, Qin Hu3, Qiang Zhang4, Guan-Yue Su5, Hong-Mei Xiao1,2, Bo-Yang Li1,2, Wen-Di Shen1,2, Xiang Qiu1,2, Wan-Qiang Lv1,2 and Hong-Wen Deng1,2,6* 1Center of System Biology and Data Information, School of Basic Medical Science, Central South University, Changsha, China 2Center of Reproductive Health, School of Basic Medical Science, Central South University, Changsha, China 3Kangda College of Nanjing Medical University, Nanjing, China 4College of Public Health, Zhengzhou University, Zhengzhou, China 5Institute of Biomedical Engineering, West China School of Basic Medical Sciences and Forensic Medicine, ...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Sara AlMarabeh, Mohammed H. Abdulla and Ken D. O'Halloran* Department of Physiology, School of Medicine, College of Medicine and Health, University College Cork, Cork, Ireland Renal sensory nerves are important in the regulation of body fluid and electrolyte homeostasis, and blood pressure. Activation of renal mechanoreceptor afferents triggers a negative feedback reno-renal reflex that leads to the inhibition of sympathetic nervous outflow. Conversely, activation of renal chemoreceptor afferents elicits reflex sympathoexcitation. Dysregulation of reno-renal reflexes by suppression of the inhibitory refle...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Conclusion: This study observed an inverse correlation between plasma LDL cholesterol and heart function in individuals with T2DM. Patients with higher levels of plasma LDL cholesterol had worse left ventricular function. Therefore, plasma LDL cholesterol may be a modifiable risk factor of heart failure in diabetes, but prospective studies are necessary to confirm this finding. Introduction Type 2 diabetes mellitus (T2DM) is a metabolic disease that affects a considerable number of patients worldwide (1). Among diabetic individuals, cardiovascular disease (CVD) is the leading cause of morbidity and mortality (2). C...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
In conclusion, both RH and RfH constitute challenges in clinical practice and should be addressed as distinct clinical entities by trained professionals who are capable to identify comorbidities and provide specific, diversified, and individualized treatment. PMID: 30525180 [PubMed - as supplied by publisher]
Source: Jornal Brasileiro de Nefrologia - Category: Urology & Nephrology Tags: J Bras Nefrol Source Type: research
Authors: Martin WP, Docherty NG, Le Roux CW Abstract INTRODUCTION: Cardiovascular and renal disease accounts for a substantial proportion of the morbidity and mortality associated with obesity and type 2 diabetes mellitus (T2DM). Bariatric surgery is associated with improved long-term cardiovascular and renal outcomes. Areas covered: All major case-control, cohort, and randomized controlled trial studies of bariatric surgery in adults with T2DM were screened and data on prespecified cardiovascular and renal outcomes collated. Bariatric surgery reduces all-cause mortality and risk of cardiovascular disease, albuminu...
Source: Expert Review of Endocrinology and Metabolism - Category: Endocrinology Tags: Expert Rev Endocrinol Metab Source Type: research
In conclusion, in the Framingham Heart Study population, in the last 30 years, disease duration in persons with dementia has decreased. However, age-adjusted mortality risk has slightly decreased after 1977-1983. Consequences of such trends on dementia prevalence should be investigated. Recent Research on the Benefits of Exercise in Later Life https://www.fightaging.org/archives/2018/04/recent-research-on-the-benefits-of-exercise-in-later-life/ A sizable body of work points to the ability of older individuals to continue to obtain benefits through regular physical activity, and particularly in the case ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In conclusion, decreases in BP in response to CPAP in patients with in diabetic CKD, despite maintained high MSNA, indicate other mechanism contributing to HTN in these patients as well as other central sympathoexcitatory pathways activated.
Source: Hypertension - Category: Cardiology Authors: Tags: Oral Abstract Presentations Source Type: research
AbstractPurpose of ReviewThe review assesses the role of non-pharmacologic therapy for obesity and chronic kidney disease (CKD) associated refractory hypertension (rf HTN).Recent FindingsHypertensive 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.SummaryCurrent evidence advocates for a greater role of bariatric surgery in...
Source: Current Hypertension Reports - Category: Primary Care Source Type: research
AbstractPurpose of ReviewThe etiology of hypertension, a critical public health issue affecting one in three US adults, involves the integration of the actions of multiple organ systems, including the renal sympathetic nerves. The renal sympathetic nerves, which are comprised of both afferent (sensory input) and efferent (sympathetic outflow) arms, have emerged as a major potential therapeutic target to treat hypertension and disease states exhibiting excess renal sympathetic activity.Recent FindingsThis review highlights recent advances in both clinical and basic science that have provided new insight into the distributio...
Source: Current Hypertension Reports - Category: Primary Care Source Type: research
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