Submitted on June 1, 2004
Accepted on August 9, 2004
Chronic 
-Adrenoreceptor-Activation Increases Cardiac Cavity Size Through Chamber Remodeling and not Modifications in Myocardial Material Properties
Mark Gibbs1, Demetri GA Veliotes1, Christopher Anamourlis1, Danelle Badenhorst1, Oleg Osadchii1, Gavin R Norton1, and Angela J Woodiwiss1*
1 Physiology, University of the Witwatersrand, Johannesburg, Gauteng, South Africa
* To whom correspondence should be addressed. E-mail: woodiwissaj{at}physiology.wits.ac.za.
Chronic 
-adrenoreceptor (-AR) activation increases left ventricular (LV) cavity size by promoting a right shift in LV diastolic pressure-volume (P-V) relations in association with increases in myocardial collagen concentrations with a low tensile strength (non-cross-linked collagen). As diastolic P-V relations are determined by chamber remodeling as well as by myocardial material properties (indexed by myocardial stiffness), both of which are associated with modifications in myocardial collagen cross-linking, we evaluated whether chamber remodeling or alterations in myocardial material properties govern -AR-mediated modifications in diastolic P-V relations. The effect of chronic administration of isoproterenol (ISO at 0.04 mg.kg-1.day-1 from 12 to 19 months of age) to spontaneously hypertensive rats (SHR) on LV cavity dimensions, LV diastolic P-V relations, myocardial collagen characteristics, myocardial stiffness constants (k, slope of the LV diastolic stress-strain relation) and LV chamber and myocardial systolic function was assessed. SHR at 19 months of age had normal LV diastolic P-V relations, marked myocardial fibrosis (pathological score), increases in myocardial cross-linked (insoluble to cyanogen bromide digestion), type I and type III collagen concentrations and an enhanced myocardial k. ISO administration to SHR resulted in enlarged LV cavity dimensions mediated by a right shift in LV diastolic P-V relations, an increased volume intercept of the LV diastolic P-V relation, a decreased LV relative wall thickness despite a tendency to augment LV hypertrophy, and increased non-cross-linked, type I and type III myocardial collagen concentrations. ISO administration resulted in a reduced pump function without modifying intrinsic myocardial systolic function. However, despite increasing myocardial non-cross-linked concentrations, ISO failed to alter myocardial k in SHR. These results suggest that -AR-mediated right shifts in LV diastolic P-V relations, a change which induces a decrease in pump function, is mediated by chamber remodeling, but not by modifications in myocardial material properties.
