This Article Full Text Full Text (PDF) All Versions of this Article: 41/3/499    most recent 01.HYP.0000056601.29613.DDv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Badenhorst, D. Articles by Norton, G. R. Search for Related Content PubMed PubMed Citation Articles by Badenhorst, D. Articles by Norton, G. R.

(Hypertension. 2003;41:499.)
© 2003 American Heart Association, Inc.

Scientific Contributions

ß-Adrenergic Activation Initiates Chamber Dilatation in Concentric Hypertrophy

Danelle Badenhorst; Demetri Veliotes; Muzi Maseko; Oupa J. Tsotetsi; Richard Brooksbank; Alvin Naidoo; Angela J. Woodiwiss; 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.

Correspondence to Gavin R. Norton and Angela J. Woodiwiss, School of Physiology, University of the Witwatersrand Medical School, 7 York Rd, Parktown, 2193 Johannesburg, South Africa. E-mail woodiwissaj{at}physiology.wits.ac.za

It is uncertain whether chronic ß-adrenoreceptor (ß-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 ß-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: ß-adrenergic • hypertrophy • remodeling • cardiac dysfunction • collagen

This article has been cited by other articles:

				R. Berni, M. Savi, L. Bocchi, F. Delucchi, E. Musso, C. Chaponnier, G. Gabbiani, S. Clement, and D. Stilli Modulation of actin isoform expression before the transition from experimental compensated pressure-overload cardiac hypertrophy to decompensation Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1625 - H1632. [Abstract] [Full Text] [PDF]

				O. E. Osadchii, G. R. Norton, R. McKechnie, D. Deftereos, and A. J. Woodiwiss Cardiac dilatation and pump dysfunction without intrinsic myocardial systolic failure following chronic beta-adrenoreceptor activation Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1898 - H1905. [Abstract] [Full Text] [PDF]

				M. Baek and M. Weiss Down-Regulation of Na+ Pump {alpha}2 Isoform in Isoprenaline-Induced Cardiac Hypertrophy in Rat: Evidence for Increased Receptor Binding Affinity but Reduced Inotropic Potency of Digoxin J. Pharmacol. Exp. Ther., May 1, 2005; 313(2): 731 - 739. [Abstract] [Full Text] [PDF]

				D. G.A. Veliotes, A. J. Woodiwiss, D. A.J. Deftereos, D. Gray, O. Osadchii, and G. R. Norton Aldosterone Receptor Blockade Prevents the Transition to Cardiac Pump Dysfunction Induced by {beta}-Adrenoreceptor Activation Hypertension, May 1, 2005; 45(5): 914 - 920. [Abstract] [Full Text] [PDF]

				M. Gibbs, D. G. A. Veliotes, C. Anamourlis, D. Badenhorst, O. Osadchii, G. R. Norton, and A. J. Woodiwiss Chronic {beta}-adrenoreceptor activation increases cardiac cavity size through chamber remodeling and not via modifications in myocardial material properties Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2762 - H2767. [Abstract] [Full Text] [PDF]