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Rosiglitazone treatment restores renal responsiveness to atrial natriuretic peptide in rats with congestive heart failure.
- Source :
-
Journal of cellular and molecular medicine [J Cell Mol Med] 2019 Jul; Vol. 23 (7), pp. 4779-4794. Date of Electronic Publication: 2019 May 13. - Publication Year :
- 2019
-
Abstract
- The thiazolidinedione (TZD) class of Peroxisome proliferator-activated receptor gamma agonists has restricted clinical use for diabetes mellitus due to fluid retention and potential cardiovascular risks. These side effects are attributed in part to direct salt-retaining effect of TZDs at the renal collecting duct. A recent study from our group revealed that prolonged rosiglitazone (RGZ) treatment caused no Na+/H <subscript>2</subscript> O retention or up-regulation of Na <superscript>+</superscript> transport-linked channels/transporters in experimental congestive heart failure (CHF) induced by surgical aorto-caval fistula (ACF). The present study examines the effects of RGZ on renal and cardiac responses to atrial natriuretic peptide (ANP), Acetylcholine (Ach) and S-Nitroso-N-acetylpenicillamine (SNAP-NO donor). Furthermore, we assessed the impact of RGZ on gene expression related to the ANP signalling pathway in animals with ACF. Rats subjected to ACF (or sham) were treated with either RGZ (30 mg/kg/day) or vehicle for 4 weeks. Cardiac chambers pressures and volumes were assessed invasively via Miller catheter. Kidney excretory and renal hemodynamic in response to ANP, Ach and SNAP were examined. Renal clearance along with cyclic guanosine monophosphate (cGMP), gene expression of renal CHF-related genes and ANP signalling in the kidney were determined. RGZ-treated CHF rats exhibited significant improvement in the natriuretic responses to ANP infusion. This 'sensitization' to ANP was not associated with increases in neither urinary cGMP nor in vitro cGMP production. However, RGZ caused down-regulation of several genes in the renal cortex (Ace, Nos3 and Npr1) and up-regulation of ACE2, Agtrla, Mme and Cftr along down-regulation of Avpr2, Npr1,2, Nos3 and Pde3 in the medulla. In conclusion, CHF+RGZ rats exhibited significant enhancement in the natriuretic responses to ANP infusion, which are known to be blunted in CHF. This 'sensitization' to ANP is independent of cGMP signalling, yet may involve post-cGMP signalling target genes such as ACE2, CFTR and V2 receptor. The possibility that TZD treatment in uncomplicated CHF may be less detrimental than thought before deserves additional investigations.<br /> (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)
- Subjects :
- Acetylcholine pharmacology
Animals
Atrial Natriuretic Factor administration & dosage
Blood Pressure drug effects
Cyclic GMP metabolism
Endothelium drug effects
Gene Expression Regulation drug effects
Heart Failure pathology
Hemodynamics drug effects
Kidney drug effects
Male
Rats, Sprague-Dawley
Rosiglitazone pharmacology
Signal Transduction drug effects
Vasodilation drug effects
Atrial Natriuretic Factor therapeutic use
Heart Failure drug therapy
Kidney pathology
Rosiglitazone therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1582-4934
- Volume :
- 23
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Journal of cellular and molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 31087547
- Full Text :
- https://doi.org/10.1111/jcmm.14366