Attenuated β-adrenoceptor-mediated cardiac contractile responses following androgenic steroid administration to sedentary rats

Abstract

Androgenic steroids administered in doses at pharmacological levels to sedentary animals have been shown to result in a reduced β-adrenoceptor-mediated increase in systolic cardiac performance when assessed in vivo. Whether the attenuated adrenergic response occurs as a consequence of alterations in either cardiac loads, heart rate, modifications in left ventricular (LV) geometry, or a decrease in myocardial contractile performance has not been determined. In this study the effect of chronic administration (over 3 months) of an androgenic steroid (nandrolone decanoate, 5 mg · kg⁻¹ biweekly) on the response of load-insensitive indices of myocardial contractile function [the slope of the LV systolic stress-strain relationship (LV-Eⁿ _max, where Eⁿ _max is systolic myocardial elastance)] to an adrenergic-inotropic stimulus was examined ex vivo in paced rat hearts. Systolic cardiac performance was assessed at 300 beats · min⁻¹ in isolated constant flow perfused heart preparations both before and during 10^−8.5 mol · l⁻¹ isoproterenol (ISO) infusion (approximate concentration of ISO eliciting 50% maximal inotropic response to ISO). Steroid administration resulted in left-shifted LV systolic and diastolic pressure-volume (P-V ) relationships. The leftshifted P-V relationships were attributed, in part, to increased slopes of these relationships. However, the steroid-mediated increment in the slope of the systolic P-V relationship (systolic chamber elastance, E_max) was not associated with a similar change in LV Eⁿ _max [control 19.2 (SEM 2.1) g · cm⁻², steroid 18.3 (SEM 2.4) g . cm⁻²] as determined in the absence of ISO. Isoproterenol infusion resulted in an increase in both E_max and Eⁿ _max in the control rats, without altering systolic performance in the steroid treated rats. Consequently, in the presence of ISO, the steroid treated rats exhibited a similar E_max, but a reduction in Eⁿ _max compared to the control rats [control 25.6 (SEM 1.9) g · cm⁻², steroid 18.5 (SEM 1.5) g · cm⁻²; P < 0.05]. In conclusion, these results would suggest that chronic high dose androgenic steroid administration produces a decrease in myocardial contractile reserve to β-adrenoceptor stimulation.