Published Online
on February 17, 2003

A more recent version of this article appeared on March 1, 2003

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Submitted on August 6, 2002
Revised on August 26, 2002

-Adrenergic Activation Initiates Chamber Dilatation in Concentric Hypertrophy

Danelle Badenhorst; Demetri Veliotes; Muzi Maseko; Oupa J. Tsotetsi; Richard Brooksbank; Alvin Naidoo; Angela J. Woodiwiss^*; and Gavin R. Norton

From the Cardiovascular Pathophysiology Research Unit, School of Physiology, University of the Witwatersrand Medical School (D.B., D.V., M.M., O.J.T., R.B., A.N., A.J.W., G.R.N.), Johannesburg, South Africa; and the Department of Physiology, Medical University of South Africa (O.J.T.), Johannesburg, South Africa.

^* To whom correspondence should be addressed. E-mail: woodiwissaj{at}physiology.wits.ac.za.

Abstract--It is uncertain whether chronic -adrenoreceptor (-AR)-activation in hypertension could initiate the progression from compensated left ventricular (LV) hypertrophy to pump dysfunction. It is also uncertain if this effect is through adverse LV remodeling (chamber dilatation with wall thinning and pump dysfunction) or intrinsic myocardial contractile dysfunction. We evaluated the effect of 5 months of isoprenaline (0.02 mg · kg^-1 · d^-1) on hemodynamics, LV wall thickness, cavity size, and interstitial characteristics in spontaneously hypertensive rats (SHR) with compensated LV hypertrophy. In the absence of myocyte necrosis, changes in volume preload, pressure afterload, and heart rate or decreases in baseline systolic myocardial elastance (load independent measure of intrinsic myocardial contractility), ISO produced a right shift in LV diastolic pressure-volume (P-V) relations (chamber dilatation), a decrease in LV wall thickness despite a further increase in LV weight in SHR, LV pump dysfunction (right shift in LV systolic P-V relations), and deleterious interstitial remodeling (increments in total and noncrosslinked myocardial collagen concentrations). The isoprenaline-induced LV geometric, chamber performance, and interstitial changes were similar to alterations noted during decompensation in older SHR. In summary, in the absence of tissue necrosis and baseline intrinsic myocardial contractile dysfunction, chronic -AR activation induces interstitial and chamber remodeling and, hence, pump dysfunction. These data suggest that chronic sympathetic activation initiates the progression from compensated concentric LV hypertrophy in hypertension to cardiac dysfunction primarily through deleterious cardiac remodeling rather than intrinsic myocardial contractile dysfunction.

Key words: -adrenergic • hypertrophy • remodeling • cardiac dysfunction • collagen

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