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(Hypertension. 2008;51:289.)
© 2008 American Heart Association, Inc.

Original Articles

Mineralocorticoid Signaling in Transition to Heart Failure With Normal Ejection Fraction

Brian P. Shapiro; Theophilus E. Owan; Selma Mohammed; Martina Kruger; Wolfgang A. Linke; John C. Burnett, Jr; Margaret M. Redfield

From the Division of Cardiovascular Diseases (B.P.S., S.M., J.C.B., M.M.R.), Mayo Clinic and Foundation, Rochester, Minn; Division of Cardiology (T.E.O.), University of Utah, Salt Lake City; and the Physiology and Biophysics Unit (M.K., W.A.L.), University of Muenster, Muenster, Germany.

Correspondence to Margaret M. Redfield, Mayo Cardiorenal Research Laboratory, 200 First St SW, Rochester, MN 55905. E-mail redfield.margaret{at}mayo.edu

Heart failure with normal ejection fraction occurs in elderly patients with hypertensive heart disease. We hypothesized that, in such patients, mineralocorticoid receptor activation accelerates the types of ventricular and vascular remodeling and dysfunction believed important in the transition to heart failure. We tested this hypothesis by administering deoxycorticosterone acetate (DOCA) without salt loading or nephrectomy to elderly dogs with experimental hypertension. Elderly dogs were made hypertensive by renal wrapping. After 5 weeks, dogs were randomly assigned to DOCA (1 mg/kg per day IM; old hypertensive [OH]+DOCA; n=11) or not (OH; n=11) for 3 weeks. At week 8, conscious echocardiography and hemodynamic assessment under anesthesia were performed. DOCA resulted in further increases in conscious blood pressure (P<0.05) without increases in cardiac output or diastolic volume. In the conscious state, effective arterial elastance (P<0.05) and systemic vascular resistance (P=0.06) were increased, and systemic arterial compliance (P<0.05) was decreased in OH+DOCA animals. After anesthesia, instrumentation, and autonomic blockade, blood pressure was lower, whereas left ventricular (LV) systolic elastance, LV diastolic stiffness, and ex vivo myofiber diastolic stiffness were increased in OH+DOCA animals. LV collagen was increased in OH+DOCA animals (P<0.05 for all), but LV mass, LV brain natriuretic peptide, and titin isoform profiles were not. Neither aortic stiffness nor aortic structure was altered in OH+DOCA animals. These findings suggest that age and hypertensive heart disease enhance sensitivity to exogenous mineralocorticoid administration and that mineralocorticoid receptor activation could contribute to the transition to heart failure in elderly persons by promoting increases in LV diastolic and systolic stiffness.

Key Words: heart failure • hypertension • collagen • diastole

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