Endocrine hypertension
Philip E. Harris, Pierre-Marc G. Bouloux in Endocrinology in Clinical Practice, 2014
Although several corticosteroids produced by the adrenal gland have mineralocorticoid function (Figure 21.2), aldosterone is the most potent and predominant human mineralocorticoid. Aldosterone binds to the mineralocorticoid receptor (MR), a nuclear hormone receptor, and causes it to translocate to the nucleus, interact with the respective response elements, and induce a change in transcriptional activity that leads to an increase in activity of the epithelial sodium channel in the distal convoluted tubule (DCT) (Figure 21.3).2 Excess mineralocorticoid results in retention of sodium chloride and water, with obligate loss of potassium and hydrogen ions to maintain electrical neutrality. The resultant clinical picture is of hypertension, metabolic alkalosis, and hypokalemia.
Management of Hypertension in Heart Failure
Andreas P. Kalogeropoulos, Hal A. Skopicki, Javed Butler in Heart Failure, 2023
MRAs inhibit aldosterone's activation of the epithelial sodium channel. Through this mechanism, MRAs inhibit sodium retention, endothelial dysfunction, vasoconstriction, vascular remodeling, and fibrosis.72 For patients with HFpEF in the TOPCAT study,73 spironolactone did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes or hospitalization. There was, however, a significant reduction in hospitalization for HF in the Americas, where the protocol was followed more rigorously.74 Based on these results, the 2017 ACC/AHA/HFSA guideline update added new recommendations for the use of MRAs in the management of HFpEF.71 Third-generation MRAs, including finerenone and canrenone, are non-steroidal compounds with both high selectivity and high potency to inhibit the mineralocorticoid receptor, enhanced concentration in both the kidney and heart (spironolactone and eplerenone remain primarily in the kidney) with beneficial effects on progressive myocardial fibrosis and potentially lower incidence of hyperkalemia.75 The FINEARTS-HF study will assess the role of finerenone on reduction of cardiovascular death and HF events, including HF hospitalizations and urgent visits with HF issues in patients with HFpEF.76
The Treatment of Hypertension with Nutrition, Nutritional Supplements, Lifestyle and Pharmacologic Therapies
Stephen T. Sinatra, Mark C. Houston in Nutritional and Integrative Strategies in Cardiovascular Medicine, 2022
Increased dietary sodium intake is associated with hypertension, cerebrovascular accident (CVA), left ventricular hypertrophy (LVH), diastolic dysfunction (DD), CHD, MI, renal insufficiency, proteinuria, arterial stiffness, platelet dysfunction and increased sympathetic nervous system (SNS) activation. A reduction in dietary sodium intake lowers BP and the risk of all of these diseases [2–5,10–15,18,19,53–61]. Decreasing dietary sodium intake in hypertensive patients, especially in the salt-sensitive patients and those with an overactive renal epithelial sodium channel, lowers BP by 4–6/2–3 mmHg proportional to the amount of sodium restriction, reduces the intravascular volume, and may prevent or delay hypertension in high-risk patients [54].
Flucloxacillin-induced hypokalaemia: a case report
Published in Acta Clinica Belgica, 2018
To understand the action of flucloxacillin on the collecting duct, a general notice of physiology is required. In the collecting duct, two main cell types responsible for water and ion transport are the intercalated and principal cells [9,10]. The ion and water transport is highly regulated by a wide variety of stimuli, making fine tuning possible. In the principal cell, electrogenic sodium (Na+) transport is mediated through the epithelial sodium channel (ENaC) and is co-ordinated by aldosterone [10]. The sodium (Na+) transport (from luminal to intracellular) generates a transmembrane voltage potential, which is negative on the luminal side. This transmembrane potential generates the driving force for potassium (K+) secretion by renal outer medullary potassium (ROMK) channels and Big Potassium (BK) channels [10]. Besides, this enhances hydrogen (H+) secretion by the adjacent intercalated cells and chloride (Cl−) reabsorption [11].
Emerging medicines to improve the basic defect in cystic fibrosis
Published in Expert Opinion on Emerging Drugs, 2022
Isabelle Fajac, Isabelle Sermet-Gaudelus
The CFTR protein is expressed at the apical membrane of many epithelial cells with direct relationships between abnormal expression or function, and CF pathology. When open or activated, the CFTR channel allows passive diffusion of chloride and bicarbonate ions down their electrochemical gradient. It has also many other roles such as inhibition of sodium transport through the epithelial sodium channel and regulation of other chloride channels [8]. CFTR mutations lead to a loss of CFTR activity due to either reduced quantity or impaired function of the protein. In the airways, a defective CFTR protein leads to impaired mucociliary clearance, infection and inflammation, bronchiectasis, and respiratory failure. To date, around 2,000 CFTR mutations have been described and around 250 variants have evidence supporting a disease-causing effect [9]. In the last decade, very innovative drugs called CFTR modulators that improve the defective CFTR protein function have been approved for marketing in patients with CF.
The role of dietary salt and alcohol use reduction in the management of hypertension
Published in Expert Review of Cardiovascular Therapy, 2021
According to the theoretical description, hypertension could result from a rise in cardiac output or in total peripheral resistance, or both. The evidence has proposed that excessive sodium retention is a contributing factor in genetically predisposed (salt-sensitive) persons [46]. Sodium sensitivity is the responsiveness of BP to the variations in salt ingestion. The degree of BP variation after sudden variations in salt ingestion differs significantly from person to person [161,162]. The diminished kidney sodium excretion can cause the preliminary volume increase and afterward, it will lead to hypertension [163,164]. The way by which sodium reabsorption rise is not well known. The probable mechanism of action includes; the thick ascending limb Na-K-2Cl cotransporter, raised an action of the proximal tubular Na-H exchanger, the distal tubular Na-Cl cotransporter, and the collecting duct epithelial sodium channel [165–167]. The association between hypertension and the activity of the proximal Na-H exchanger has been supported by evidence [166]. The raised action of the epithelial sodium channel in the collecting tubule is blamed for hypertension [167]. The abnormality of a bidirectional sodium-calcium exchanger leads to enlarged calcium entrance into the smooth muscle of the blood vessel in reply to excessive sodium ingestion. The raised calcium entrance leads to vasoconstriction and hypertension as evidence by a study conducted on sodium-sensitive hypertensive rats and transgenic mice [168,169].
Related Knowledge Centers
- Collecting Duct System
- Nephron
- Sodium
- Ion Channel
- Ion
- Scnn1A
- Scnn1B
- Scnn1G
- Scnn1D
- Kidney