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Abstract

The spontaneously hypertensive rat (SHR) is an animal model of genetic hypertension which develops heart failure with aging, similar to man. The consistent pattern of a long period of stable hypertrophy followed by a transition to failure provides a useful model to study mechanisms of heart failure with aging and test treatments at differing phases of the disease process. The transition from compensated hypertrophy to failure is accompanied by changes in cardiac function which are associated with altered active and passive mechanical properties of myocardial tissue; these events define the physiologic basis for cardiac decompensation. In examining the mechanism for myocardial tissue dysfunction, studies have demonstrated a central role for neurohormonal activation, and specifically the renin-angiotensin-aldosterone system. Pharmacologic attenuation of this system at differing points in the course of the process suggests that prevention but not reversal of myocardial tissue dysfunction is possible. The roles of the extracellular matrix, apoptosis, intracellular calcium, beta-adrenergic stimulation, microtubules, and oxygen supply-demand relationships in ultimately mediating myocardial tissue dysfunction are reviewed. Studies suggest that while considerable progress has been made in understanding and treating the transition to failure, our current state of knowledge is limited in scope and we are not yet able to define specific mechanisms responsible for tissue dysfunction. It will be necessary to integrate information on the roles of newly discovered, and as yet undiscovered, genes and pathways to provide a clearer understanding of maladaptive remodeling seen with heart failure. Understanding the mechanism for tissue dysfunction is likely to result in more effective treatments for the prevention and reversal of heart failure with aging. It is anticipated that the SHR model will assist us in reaching these important goals.

Longitudinal Evaluation of Fatty Acid Metabolism in Normal and Spontaneously Hypertensive Rat Hearts with Dynamic MicroSPECT Imaging

“…Even with species differences, our results (here for fatty acid metabolism, and [6, 7] for glucose metabolism) and other results obtained with the SHR model [38–40] corroborate studies in humans, which show that there are abnormalities in myocardial metabolic function manifested by reduced rates of fatty acid utilization and oxidation and an increase in glucose metabolism associated with hypertension-induced left ventricular hypertrophy (LVH) and idiopathic cardiomyopathy [21, 41]. In a separate positron emission tomography (PET) study imaging 18 F-fluorodeoxyglucose (FDG) with use of a microPET scanner, we observed that glucose metabolism in the SHR model was greater than that in the WKY control [6, 7], and that the glucose metabolism in both decreased with age.…”

Imaging cardiac SCN5A using the novel F-18 radiotracer radiocaine

“…Even though not significant in our sample groups, there seems to be a trend between the two healthy groups NF1 and NF2 as signal reduces with age. Since the prevalence of arrhythmias, conduction disturbances, and heart failure all increase with age, it will be interesting to measure how the radiocaine-SCN5A signal changes in longitudinal studies of the aging process 21 .…”

Active components from Radix Scrophulariae inhibits the ventricular remodeling induced by hypertension in rats

“…SHR is a useful experimental model of essential hypertension (Boluyt and Bing 2000 ; Bing et al 2002 ). SHRs are characterized by the fact that they suffer from pre-hypertension during the first 6–8 weeks of their life and then develop many features of hypertensive end-organ damage: cardiac hypertrophy, cardiac failure and so on (Abbate et al 2006 ).…”