Impact of gender on adrenergic-induced cardiac dilatation and systolic dysfunction in spontaneously hypertensive rats
Magubane, Mhlengi Mthokozisi
Left ventricular hypertrophy (LVH) is more frequently associated with LV dilatation and systolic chamber dysfunction in males than in females. The mechanisms of this effect are uncertain. As excessive adrenergic stimulation may be responsible for LV dilatation and systolic chamber dysfunction in hypertension, in my dissertation I aimed to assess whether gender determines the adverse effects on LV chamber remodeling following 6 months of daily β-adrenergic receptor (AR) stimulation (isoproterenol [ISO] at 0.04 mg.kg-1day-1) in spontaneously hypertensive rats (SHR). LV dilatation was assessed in vivo from LV end diastolic diameter (EDD) (echocardiography) and ex vivo from the volume intercept at 0 mm Hg pressure (V0) of the LV diastolic pressure-volume relationship (isolated, perfused heart technique). LV systolic function was determined in vivo from LV endocardial fractional shortening (FSend) and ex vivo from the slope (LV end systolic elastance [LV Ees]) of the LV end systolic pressure-volume relationship (isolated, perfused heart technique). As compared to saline-treated male SHR (n=13), male SHR receiving ISO for 6 months (n=13) developed an increased LV EDD (Male Saline: 6.56±0.20 mm; Male ISO: 7.78±0.29 mm; p<0.05) and LV V0 (Male Saline: 0.22±0.01 ml; Male ISO: 0.31±0.02 ml; p<0.05). In contrast, ISO administration failed to modify LV EDD (Female Saline, n=13: 6.06±0.15 mm; Female ISO, n=12: 6.33±0.15 mm) or LV V0 (Female Saline: 0.17±0.01ml; Female ISO: 0.17±0.01 ml) in female SHR. In addition, there was a gender-ISO interactive effect on LV Ees (p<0.05; Male Saline: 2268±336 mmHg.ml-1; Male ISO: 1623±164 mmHg.ml-1; Female Saline: 1910±219 mmHg.ml-1; Female ISO: 2302±230 mmHg.ml-1). In conclusion, as compared to female SHR, male SHR are more susceptible to the adverse effects of chronic β-AR activation on LV cavity dimensions and systolic chamber function. These results suggest that the higher prevalence of LV dilatation and systolic chamber dysfunction in males than in females with LVH may be attributed to an increased susceptibility to the adverse effects of adrenergic stimulation.