An association between alterations in LVED k and collagen solubility but not between changes in LVED k and total collagen or phenotype ratios after antihypertensive therapy in SHRs suggests that myocardial stiffness in hypertension is the consequence of an enhanced myocardial collagen cross-linking rather than of an increase in total collagen or type I phenotype concentrations.

The effect of chronic administration of an androgenic steroid on left ventricular (LV) compliance and contractility was studied in rats. Rats received a biweekly intramuscular injection of nandrolone decanoate (5 mg/kg; steroid group) or the vehicle (control group) for 3 mo. Cardiac performance was measured in anesthetized open-chest ventilated rats. LV compliance was determined from the slope of the LV end-diastolic pressure (LVEDP) vs. LV end-diastolic (LVED) strain relation measured in the long and short axes of the LV. LV regional myocardial compliance was determined from the slope of the LVED stress vs. LVED strain relation (myocardial elastic stiffness constant). Cardiac contractility was determined from the slope of the LV end-systolic (LVES) pressure vs. LVES strain relation. Systolic performance was also assessed from the slope of the pressure-length area (PL area) or stroke work vs. LVED strain and LVEDP relations. Nandrolone decanoate decreased body weight, heart weight, and plasma testosterone concentrations but increased the heart weight-to-body weight ratio. Nandrolone decanoate decreased LV compliance (slope of LVEDP vs. LVED strain relation in long and short axes; steroid vs. control, P < 0.01). This occurred as a result of an increased regional myocardial stiffness (myocardial elastic stiffness constant; steroid vs. control, P < 0.01), which resulted in a reduced cardiac systolic performance (PL area vs. LVEDP, slope of steroid vs. control group, P < 0.005). Diastolic geometry (LV wall thickness-to-radius ratio) and cardiac contractility were unchanged with steroid administration. In conclusion, chronic administration of the androgenic steroid nandrolone decanoate decreases LV myocardial compliance and thus overall cardiac performance without altering contractility in rats.

Androgenic steroids administered in doses at pharmacological levels to sedentary animals have been shown to result in a reduced beta-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-E(n)(max), where E(n)(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 E(n)(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 E(n)(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 E(n)(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 beta-adrenoceptor stimulation.

Habitual exercise results in a rightward shift in left ventricular end diastolic (LVED) pressure-volume or internal dimension (P-D) relationships [left ventricular (LV) remodeling]. However, exercise-mediated LV hypertrophy (LVH) produces an increased LV relative wall thickness [ratio (h/r) of wall thickness (h) to internal radius (r)] and hence a decrement in diastolic wall stress despite LV remodeling. In this study, the effect of chronic administration of an androgenic steroid on exercise-induced LV remodeling and h/r was examined in rats. Habitual exercise on voluntary running wheels resulted in LVH and a rightward shift in the LVED P-D relationships. However, LVH was sufficient to increase LVED h/r. Androgenic steroid administration to exercised rats, without influencing the development of exercise-induced LVH, produced a further rightward shift in the LVED P-D relationship associated with an increased diameter intercept. As a consequence, LVED h/r was reduced to control values. The steroid-mediated effects were not associated with alterations in either the quantity or quality of LV collagen. In conclusion, high-dose androgenic steroid administration alters exercise-induced LV remodeling and subsequently reduces the beneficial effect of physiological LVH on LV h/r.