title: Beta-adrenergic activation initiates chamber dilatation in concentric hypertrophy.
abstract: It is uncertain whether chronic beta-adrenoreceptor (beta-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 x kg(-1) x 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 beta-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.
authors.affiliation: Cardiovascular Pathophysiology Research Unit, School of Physiology, University of the Witwatersrand Medical School, 7 York Rd, Parktown, 2193 Johannesburg, South Africa.
authors.forename: Danelle
authors.initials: D
authors.lastname: Badenhorst
authors.forename: Demetri
authors.initials: D
authors.lastname: Veliotes
authors.forename: Muzi
authors.initials: M
authors.lastname: Maseko
authors.forename: Oupa J
authors.initials: OJ
authors.lastname: Tsotetsi
authors.forename: Richard
authors.initials: R
authors.lastname: Brooksbank
authors.forename: Alvin
authors.initials: A
authors.lastname: Naidoo
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Woodiwiss
authors.forename: Gavin R
authors.initials: GR
authors.lastname: Norton
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003094:Collagen / Q000032:analysis; D004108:Dilatation, Pathologic / Q000139:chemically induced; D018450:Disease Progression; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000473:pathology* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000473:pathology* / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000737:chemistry; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D000318:Adrenergic beta-Agonists; D003094:Collagen; D007545:Isoproterenol