Abstract 2570: Aldosterone Agonist Enhances Ventricular but Not Vascular Stiffness in an Aged Canine Model of Hypertensive Heart Disease
Body: Aldosterone is postulated to contribute to the pathogenesis of heart failure (HF) with normal ejection fraction (EF). We tested this hypothesis by administering DOCA (an aldosterone agonist) to elderly canines with experimental hypertension and determining whether it accelerated ventricular dysfunction and if so, by what mechanism.
Methods: Old dogs (n = 22, age 8 to 12 years) with chronic hypertension due to renal wrapping, a model characterized by normal EF, LV hypertrophy, LV fibrosis and increased aortic and LV systolic and diastolic stiffness were randomized to receive DOCA (1 mg/kg IM) weeks 6 – 8 post renal wrapping (rwHTN+DOCA, n=11) or not (rwHTN). After week 8, dogs were instrumented to measure LV systolic (Ees) and diastolic (EDPVR-β and LV volume at a common end diastolic pressure, EDV-30) elastance and the aortic elastic modulus (EM, aortic stiffness). LV and aortic collagen (hydroxyproline assay and quantitative histomorphometry), LV and aortic collagen solubility (a marker of collagen cross-linking due to glycosylation end products), change in serum procollagen III pre to post renal wrapping, LV hypertrophy (LV mass and LV ANP content), chamber remodeling (LV mass/volume ratio, LV mass/EDV) and mediators of myocyte stiffness (titin isoform expression) were assessed.
Results: See table⇓. Compared to rwHTN, rwHTN+DOCA dogs had more concentric remodeling (increased LVmass/EDV), greater diastolic (higher EDPVR-β and smaller EDV-30) and systolic (Ees) stiffness but similar aortic stiffness. While serum procollagen III and LV collagen were increased, LV and aortic collagen cross-linking, aortic collagen, LV hypertrophy, and titin isoform expression were similar.
Conclusions: Aldosterone accelerates concentric remodeling and LV systolic and diastolic stiffness in hypertensive heart disease via effects on LV fibrosis, effects which may contribute to the pathogenesis of HF with normal EF.