Abstract
Cardiovascular remodeling leading to heart failure is common in the elderly. Testing effective pharmacological treatment of human heart failure requires a suitable animal model that adequately mimics the human disease state. This study has characterized the structural, functional, and electrical characteristics of the cardiovascular system throughout the lifespan in male and female spontaneously hypertensive rats (SHRs), a genetic model of chronic hypertension-induced cardiovascular remodeling, and age- and gender-matched normotensive controls, to determine whether ageing SHRs mimic the changes seen in ageing humans. Both the ageing male and female SHRs developed progressive hypertension, ventricular hypertrophy, left ventricular fibrosis, action potential prolongation without impaired glucose tolerance. Male SHRs from 15 months of age exhibited left ventricular wall thinning and chamber dilation, together with systolic and diastolic dysfunction and increased cardiac stiffness and increased erythrocyte superoxide production, which were not present in the female SHRs. Ageing male SHRs in contrast to the female SHRs, better mimic the chronic heart failure in humans produced by chronic hypertension. Ageing male SHRs could then be used to investigate proposed therapeutic interventions for chronic congestive heart failure in humans.
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