title: Preventive and chronic mineralocorticoid receptor antagonism is highly beneficial in obese SHHF rats.
abstract: Mineralocorticoid receptor (MR) activation contributes to heart failure (HF) progression. Its overactivity in obesity is thought to accelerate cardiac remodelling and HF development. Given that MR antagonists (MRA) are beneficial in chronic HF patients, we hypothesized that early MRA treatment may target obesity-related disorders and consequently delay the development of HF.
  
  
  
  Twenty spontaneously hypertensive HF dyslipidaemic obese SHHF(cp/cp) rats and 18 non-dyslipidaemic lean SHHF(+/+) controls underwent regular monitoring for their metabolic and cardiovascular phenotypes with or without MRA treatment [eplerenone (eple), 100 mg∙kg(-1) ∙day(-1) ] from 1.5 to 12.5 months of age.
  
  
  
  Eleven months of eple treatment in obese rats (SHHF(cp/cp) eple) reduced the obesity-related metabolic disorders observed in untreated SHHF(cp/cp) rats by reducing weight gain, triglycerides and total cholesterol levels and by preserving adiponectinaemia. The MRA treatment predominantly preserved diastolic and systolic functions in obese rats by alleviating the eccentric cardiac hypertrophy observed in untreated SHHF(cp/cp) animals and preserving ejection fraction (70 ± 1 vs. 59 ± 1%). The MRA also improved survival independently of these pressure effects.
  
  
  
  Early chronic eple treatment resulted in a delay in cardiac remodelling and HF onset in both SHHF(+/+) and SHHF(cp/cp) rats, whereas SHHF(cp/cp) rats further benefited from the MRA treatment through a reduction in their obesity and dyslipidaemia. These findings suggest that preventive MRA therapy may provide greater benefits in obese patients with additional risk factors of developing cardiovascular complications.
authors.affiliation: UMRS U1116 Inserm, Nancy, France.|Fédération de Recherche 3209, Nancy, France.|Université de Lorraine, Nancy, France.|Genomics Research Unit, Luxembourg Institute of Health, Luxembourg.
authors.forename: G
authors.initials: G
authors.lastname: Youcef
authors.affiliation: UMRS U1116 Inserm, Nancy, France.|Fédération de Recherche 3209, Nancy, France.|Université de Lorraine, Nancy, France.|CHU Nancy, Nancy, France.
authors.forename: A
authors.initials: A
authors.lastname: Olivier
authors.affiliation: Genomics Research Unit, Luxembourg Institute of Health, Luxembourg.
authors.forename: N
authors.initials: N
authors.lastname: Nicot
authors.affiliation: Genomics Research Unit, Luxembourg Institute of Health, Luxembourg.
authors.forename: A
authors.initials: A
authors.lastname: Muller
authors.affiliation: Fédération de Recherche 3209, Nancy, France.|Université de Lorraine, Nancy, France.|UMR 7365 CNRS, Nancy, France.
authors.forename: C
authors.initials: C
authors.lastname: Deng
authors.affiliation: UMRS U1116 Inserm, Nancy, France.|Fédération de Recherche 3209, Nancy, France.|Université de Lorraine, Nancy, France.
authors.forename: C
authors.initials: C
authors.lastname: Labat
authors.affiliation: CHU Nancy, Nancy, France.|CIC 1433 Inserm, Pierre Drouin, Nancy, France.
authors.forename: R
authors.initials: R
authors.lastname: Fay
authors.affiliation: Fédération de Recherche 3209, Nancy, France.|Université de Lorraine, Nancy, France.|CHU Nancy, Nancy, France.|U954 Inserm, Nancy, France.
authors.forename: R-M
authors.initials: RM
authors.lastname: Rodriguez-Guéant
authors.affiliation: UMRS U1116 Inserm, Nancy, France.|CIC 1433 Inserm, Pierre Drouin, Nancy, France.
authors.forename: C
authors.initials: C
authors.lastname: Leroy
authors.affiliation: CHU Nancy, Nancy, France.|CIC 1433 Inserm, Pierre Drouin, Nancy, France.
authors.forename: F
authors.initials: F
authors.lastname: Jaisser
authors.affiliation: UMRS U1116 Inserm, Nancy, France.|Fédération de Recherche 3209, Nancy, France.|Université de Lorraine, Nancy, France.|CHU Nancy, Nancy, France.|CIC 1433 Inserm, Pierre Drouin, Nancy, France.
authors.forename: F
authors.initials: F
authors.lastname: Zannad
authors.affiliation: UMRS U1116 Inserm, Nancy, France.|Fédération de Recherche 3209, Nancy, France.|Université de Lorraine, Nancy, France.|CHU Nancy, Nancy, France.
authors.forename: P
authors.initials: P
authors.lastname: Lacolley
authors.affiliation: Genomics Research Unit, Luxembourg Institute of Health, Luxembourg.
authors.forename: L
authors.initials: L
authors.lastname: Vallar
authors.affiliation: UMRS U1116 Inserm, Nancy, France.|Fédération de Recherche 3209, Nancy, France.|Université de Lorraine, Nancy, France.|CHU Nancy, Nancy, France.|CIC 1433 Inserm, Pierre Drouin, Nancy, France.
authors.forename: A
authors.initials: A
authors.lastname: Pizard
mesh_terms: D000818:Animals; D045786:Diterpenes, Kaurane / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D009765:Obesity / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D011918:Rats, Inbred SHR; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*
chemical_list: C000598791:11alpha,12alpha-epoxyleukamenin E; D045786:Diterpenes, Kaurane; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid