Gonadally intact female rats showed less severe cardiorespiratory dysfunction and less RVLM neuronal activation compared to male rats after volume overload CHF induction.
Does sex influence cardiorespiratory dysfunction and RVLM neuro-glial remodeling in a rat model of volume overload heart failure?
Female rats exhibit resilience to cardiorespiratory dysfunction and medullary neuro-glial remodeling in volume overload heart failure compared to males, highlighting potential sex-specific pathophysiological mechanisms.
Absolute Event Rate: 0% vs 0%
Cardiorespiratory disorders, such as sympathoexcitation and disordered breathing are main hallmarks of chronic heart failure (CHF) associated with high morbidity and mortality. We recently reported RVLM catecholaminergic (C1) neurons are hyperactive in rats with CHF, contributing to cardiorespiratory distress. Notably, CHF without reductions in ejection fraction is more frequent in women than in men, but detailed sex-differences in cardiorespiratory pathophysiology, as well as the existence of a sex-dependent neurophysiological remodeling within the RVLM remain unclear. Therefore, we aimed to characterize sex-differences in cardiac, autonomic/respiratory function, RVLM C1 neuron and glial cell activation, followed by experimentally induced volume overload CHF (with preserved ejection fraction) in adult Sprague-Dawley rats. At week 8 post CHF induction, male CHF rats showed ~2.5-fold increased left ventricular dilation, while female CHF rats exhibited only ~1-fold increase. Unlike the females, both cardiac systolic (ESPVR) and diastolic function (EDPVR) were depressed in male CHF rats. Indeed, cardiomyocyte calcium handling was impaired only in CHF male rats. Cardiac arrhythmogenesis, sympathoexcitation and disordered breathing were all significant in CHF male rats but were nearly absent in female rats. Consequently, we found that RVLM C1 neurons were not chronically active in female CHF rats compared to male CHF rats. In addition, we found that male CHF rats showed clear signs of astrocyte reactivity within the RVLM region that results in shifts towards higher astrocyte complexity. The later was not present in female medullary astrocytes despite showing ventricular hypertrophy. Our results showed the gonadally intact female rats are somehow protected compared to intact male from RVLM astrocytic remodeling and chronic C1 neuronal activation following volume overload CHF, being the outcome a less severe cardiorespiratory pathology associated with the CHF phenotype.
Pereyra et al. (Mon,) reported a other. Gonadally intact female rats showed less severe cardiorespiratory dysfunction and less RVLM neuronal activation compared to male rats after volume overload CHF induction.
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