Endothelin antagonism reduces circulating galectin-3 in patients with proteinuric chronic kidney disease.

Kidney Int

University/British Heart Foundation Centre of Research Excellence, Centre of Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, UK; Department of Renal Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK. Electronic address:

Published: January 2018

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.kint.2017.10.009DOI Listing

Publication Analysis

Top Keywords

endothelin antagonism
4
antagonism reduces
4
reduces circulating
4
circulating galectin-3
4
galectin-3 patients
4
patients proteinuric
4
proteinuric chronic
4
chronic kidney
4
kidney disease
4
endothelin
1

Similar Publications

Marketed endothelin receptor antagonists (ERAs) have been associated with testicular tubular atrophy and decreases in male animal fertility in chronic toxicity studies in rats and dogs. Consistent with these findings, reduced sperm count has been observed in the clinical setting and is considered a potential class risk with chronic administration of ERAs. In contrast, no such effects on male animal fertility are noted with angiotensin II type 1 receptor blocker (ARB) treatment.

View Article and Find Full Text PDF

Introduction: Endothelin-1 (ET-1) regulates renal and vascular function, but the clinical utility of selective ET receptor antagonists has been limited due to associated fluid retention. The mechanisms underlying fluid retention remain poorly understood but could be a consequence of changes in ET-1 binding to the unantagonized ET receptor, either through increased ET-1 or non-selective ET.

Methods: A mathematical model of ET-1 kinetics was developed to quantify effects of ET antagonist exposure and selectivity on concentrations of ET-1 and its complexes with ET and ET receptors.

View Article and Find Full Text PDF

6-Nitrodopamine (6-ND) is the predominant catecholamine released from isolated vascular tissues in both mammals and reptiles, with its release being significantly reduced by the NO synthesis inhibitor, N-nitro-L-arginine methyl ester (L-NAME). The vasorelaxation induced by 6-ND is unaffected by either L-NAME or the soluble guanylate cyclase (sGC) inhibitor, ODQ, indicating an alternative mechanism of action. The vasorelaxant effect appears to be mediated through selective antagonism of dopamine D receptors rather than traditional nitric oxide (NO)-mediated pathways.

View Article and Find Full Text PDF

Background: LCZ696 (sacubitril/valsartan) antagonizes the renin-angiotensin system while simultaneously augmenting the natriuretic peptides (NPs). Inhibition of phosphodiesterase 9 inhibition (PDE9i), which hydrolyses NP-generated cGMP may be a more specific means of enhancing NP bioactivity. The objective of the present study was to compare for the first time effects of LCZ696 and PDE9i+valsartan in experimental heart failure (HF) and investigate combination PDE9i+LCZ696.

View Article and Find Full Text PDF

Exploring the Endothelin-1 pathway in chronic thromboembolic pulmonary hypertension microvasculopathy.

Sci Rep

November 2024

UMR_S 999 "Pulmonary Hypertension: Pathophysiology and Novel Therapies" (HPPIT), INSERM, Hôpital Marie Lannelongue Et Hôpital Bicêtre, Le Plessis-Robinson Et Le Kremlin-Bicêtre, France.

Targeted vasopeptide therapies have significantly advanced the management of pulmonary arterial hypertension (PAH). However, due to insufficient preclinical evidence regarding the involvement of the endothelin-1 (ET-1) pathway in chronic thromboembolic pulmonary hypertension (CTEPH) pathophysiology, the potential of ET-1 receptor antagonism in treating CTEPH remains uncertain. In this study, we investigated the role of the ET-1 pathway in CTEPH microvasculopathy using a multifaceted approach.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!