New Molecules for Treating Resistant Hypertension: a Clinical Perspective

AbstractPurpose of ReviewTo review the findings of trials evaluating pharmacological treatment approaches for hypertension in general, and resistant hypertension (RH) in particular, and propose future research and clinical directions.Recent FindingsRH is defined as blood pressure (BP) that remains above target levels despite adherence to at least three antihypertensive medications, including a diuretic. Thus far, clinical trials of pharmacological approaches in RH have focused on older molecules, with spironolactone being demonstrated as the most efficacious fourth-line agent. However, the use of spironolactone in clinical practice is hampered by its side effect profile and the risk of hyperkalaemia in important RH subgroups, such as patients with moderate-severe chronic kidney disease (CKD). Clinical trials of new molecules targeting both well-established and more recently elucidated pathophysiologic mechanisms of hypertension offer a multitude of potential treatment avenues that warrant further evaluation in the context of RH. These include selective mineralocorticoid receptor antagonists (MRAs), aldosterone synthase inhibitors (ASIs), activators of the counterregulatory renin-angiotensin-system (RAS), vaccines, neprilysin inhibitors alone and in combined formulations, natriuretic peptide receptor agonists A (NPRA-A) agonists, vasoactive intestinal peptide (VIP) agonists, centrally acting aminopeptidase A (APA|) inhibitors, antimicrobial suppression of central sympathetic o...
Source: Current Hypertension Reports - Category: Primary Care Source Type: research

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Abstract Chronic Kidney Disease (CKD) is often complicated by difficult-to-control hypertension, in part due to chronic overactivation of the sympathetic nervous system (SNS). CKD patients also exhibit a greater increase in arterial blood pressure for a given increase in sympathetic nerve activation, suggesting an augmented vasoconstrictive response to SNS activation (i.e. neurovascular transduction). One potential mechanism of increased sympathetic neurovascular transduction is heightened sensitivity of the vascular α1 adrenergic receptors (α1AR), the major effectors of vasoconstriction in response to...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - Category: Physiology Authors: Tags: Am J Physiol Regul Integr Comp Physiol Source Type: research
Background: Neuropeptide Y (NPY) is a multifaceted sympathetic neurotransmitter regulating reflex cardiovascular control, myocardial cell growth, inflammation and innate immunity. Circulating NPY levels predict cardiovascular mortality in patients with end stage kidney disease on dialysis but this relationship has never been tested in predialysis chronic kidney disease (CKD) patients. Methods: We investigated the relationship between circulating NPY and the risk for cardiovascular events (Fine &Gray competing risks model) in a cohort of 753 stages 2–5 CKD patients over a median follow-up of 36 months. Resul...
Source: Journal of Hypertension - Category: Cardiology Tags: ORIGINAL PAPERS: Epidemiology 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
Publication date: Available online 19 March 2019Source: American Journal of Kidney DiseasesAuthor(s): Elaine Ku, Benjamin J. Lee, Jenny Wei, Matthew R. WeirHypertension and chronic kidney disease (CKD) are closely interlinked pathophysiologic states, such that sustained hypertension can lead to worsening kidney function and progressive decline in kidney function can conversely lead to worsening blood pressure (BP) control. The pathophysiology of hypertension in CKD is complex and is a sequela of multiple factors, including reduced nephron mass, increased sodium retention and extracellular volume expansion, sympathetic nerv...
Source: American Journal of Kidney Diseases - Category: Urology & Nephrology Source Type: research
Publication date: Available online 2 February 2019Source: Respiratory Physiology &NeurobiologyAuthor(s): Manash Saha, Clement Menuet, Qi-Jian Sun, Peter G.R. Burke, Cara M. Hildreth, Andrew M. Allen, Jacqueline K. PhillipsAbstractRespiratory modulation of sympathetic nerve activity (respSNA) was studied in a hypertensive rodent model of chronic kidney disease (CKD) using Lewis Polycystic Kidney (LPK) rats and Lewis controls. In adult animals under in vivo anaesthetised conditions (n = 8-10/strain), respiratory modulation of splanchnic and renal nerve activity was compared under control conditions, and dur...
Source: Respiratory Physiology and Neurobiology - Category: Respiratory Medicine 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
In conclusion, acupuncture is proved to be beneficial for CKD patients. More research, however, is needed to verify the potential mechanisms. PMID: 30286626 [PubMed - in process]
Source: The American Journal of Chinese Medicine - Category: Complementary Medicine Authors: Tags: Am J Chin Med Source Type: research
Purpose of review Obstructive sleep apnea (OSA) is highly prevalent in patients with chronic kidney disease (CKD). The relationship between OSA and CKD is likely to be bi-directional. On one hand, the presence of OSA leads to intermittent hypoxia, sympathetic nervous system activity, and hypertension, all of which may have deleterious effects on kidney function. On the other hand, in patients with end-stage renal disease (ESRD), intensification of renal replacement therapy has been shown to attenuate sleep apnea severity, suggesting that the renal disease itself contributes to the pathogenesis of OSA. The present review ...
Source: Current Opinion in Pulmonary Medicine - Category: Respiratory Medicine Tags: SLEEP AND RESPIRATORY NEUROBIOLOGY: Edited by Lee Brown and Brian D. Kent Source Type: research
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