Baxdrostat and finerenone: new aldosterone synthase-aldosterone-mineralocorticoid receptor hormonal system inhibitors for the drug treatment of resistant arterial hypertension DOI Creative Commons
Kuz'min Ob, N. V. Buchneva,

V. V. Belyanin

et al.

Rational Pharmacotherapy in Cardiology, Journal Year: 2024, Volume and Issue: 20(4), P. 451 - 459

Published: Sept. 23, 2024

Resistant arterial hypertension is characterized by failure to control target blood pressure despite long-term use of optimal or maximum tolerated doses three different antihypertensive drugs, including diuretic. Patients with resistant are included in a group people at high risk cardiovascular and renal complications, accelerated progression chronic kidney disease more rapid transition the final stage disease. based on salt-sensitive, volume-dependent form hypertension, which usually occurs against background increased aldosterone production normal even decreased renin plasma activity. A key role its formation played an increase sodium reabsorption kidneys, associated excessive activity aldosterone-sensitive epithelial channels (ENaC), this ion distal segments nephron. Its assumed that pathological process, addition aldosterone, also involved small Rho GTFase Rac1 — regulatory G-protein, can enter into direct ligand-independent interaction mineralcorticoid receptors, performing function powerful nonsteroidal activator transmission their intracellular signals. Based controlled, randomized clinical trials, fourth drug overcome resistance such patients steroid receptor antagonist spironolactone. However, inclusion therapy not only fails significant proportion but significantly increases hyperkalemia, especially impaired function. The review presents data pharmacodynamics pharmacokinetics new inhibitors synthase-aldosterone-mineralocorticoid hormonal system baxdrostat finerenone, as well results studies assessing effectiveness safety profile these drugs hypertension.

Language: Английский

Protein prenylation in mechanotransduction: implications for disease and therapy DOI
Heng Chen, Jian Yang,

Qingzhen Yang

et al.

Trends in Pharmacological Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Biomechanical regulation of cell shapes promotes branching morphogenesis of the ureteric bud epithelium DOI
Kristen Kurtzeborn, Vladislav Iaroshenko, Tomáš Zárybnický

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 31, 2024

Abstract Background Branching morphogenesis orchestrates organogenesis in many tissues including kidney, where ureteric bud branching determines kidney size and nephron number. Defects result congenital renal anomalies which manifest as deviations size, function, number thus critically compromising the lifelong functional capacity established during development. Advances genetic molecular understanding of regulation have proved insufficient to improve prognosis defects. Thus, we addressed mechanisms regulating three-dimensional (3D) epithelial cell morphology shape changes novel branch initiation uncover contributions cellular mechanics on functions tissue organization normal branching-compromised tips. Methods We explored behavior at all scales by utilizing a combination mouse genetics custom machine-learning segmentation pipeline MATLAB. Ureteric shapes sizes were quantified 3D wholemount kidneys. A with live imaging fluorescently labelled UB cells, traction force microscopy, primary cells used determine how basic features niche biomechanics contribute complex point determination process that aims gaining optimal growth density limited space. Results Machine learning-based tip epithelia identified geometrical round-to-elliptical transformation key change facilitating shifts direction enable propitious complexity. Cell analyses demonstrated failure condense conformation. Analysis derived disrupted E-CADHERIN PAXILLIN mediated adhesive forces defective cytoskeletal dynamics detected fluorescent labelling actin cells. Branching-compromised showed wrinkled nuclear alterations MYH9-based microtubule organization, suggest stiff disturbed sensing response biomechanical cues. Conclusions Our results indicate within epithelium towards composed progenitors must dynamically fluctuate allow complexity arborization new formation. The data collectively propose model crowding tandem stretching transforms individual into elliptical elongated shapes. This creates local curvatures drive formation ampulla-to-asymmetric ampulla transition bud.

Language: Английский

Citations

2
Postnatal renal tubule development: roles of tubular flow and flux DOI

Yi-Jing G. Cheng,

Chien‐Chou Chen, Chih‐Jen Cheng

et al.

Current Opinion in Nephrology & Hypertension, Journal Year: 2024, Volume and Issue: 33(5), P. 518 - 525

Published: June 24, 2024

Postnatal renal tubule development is critical to adult kidney function. Several postnatal changes regulate the differentiation and proliferation of tubular cells. Here, we review literature our efforts on thick ascending limb (TAL) in Bartter syndrome (BS).

Language: Английский

Citations

0
Integrins in the kidney — beyond the matrix DOI
Fabian Bock, Shensen Li, Ambra Pozzi

et al.

Nature Reviews Nephrology, Journal Year: 2024, Volume and Issue: 21(3), P. 157 - 174

Published: Dec. 6, 2024

Language: Английский

Citations

0
Baxdrostat and finerenone: new aldosterone synthase-aldosterone-mineralocorticoid receptor hormonal system inhibitors for the drug treatment of resistant arterial hypertension DOI Creative Commons
Kuz'min Ob, N. V. Buchneva,

V. V. Belyanin

et al.

Rational Pharmacotherapy in Cardiology, Journal Year: 2024, Volume and Issue: 20(4), P. 451 - 459

Published: Sept. 23, 2024

Resistant arterial hypertension is characterized by failure to control target blood pressure despite long-term use of optimal or maximum tolerated doses three different antihypertensive drugs, including diuretic. Patients with resistant are included in a group people at high risk cardiovascular and renal complications, accelerated progression chronic kidney disease more rapid transition the final stage disease. based on salt-sensitive, volume-dependent form hypertension, which usually occurs against background increased aldosterone production normal even decreased renin plasma activity. A key role its formation played an increase sodium reabsorption kidneys, associated excessive activity aldosterone-sensitive epithelial channels (ENaC), this ion distal segments nephron. Its assumed that pathological process, addition aldosterone, also involved small Rho GTFase Rac1 — regulatory G-protein, can enter into direct ligand-independent interaction mineralcorticoid receptors, performing function powerful nonsteroidal activator transmission their intracellular signals. Based controlled, randomized clinical trials, fourth drug overcome resistance such patients steroid receptor antagonist spironolactone. However, inclusion therapy not only fails significant proportion but significantly increases hyperkalemia, especially impaired function. The review presents data pharmacodynamics pharmacokinetics new inhibitors synthase-aldosterone-mineralocorticoid hormonal system baxdrostat finerenone, as well results studies assessing effectiveness safety profile these drugs hypertension.

Language: Английский

Citations

0