Sex differences in the respiratory-sympathetic coupling in rats exposed to chronic intermittent hypoxia

Abstract

Obstructive sleep apnea (OSA) is a complex disease in which humans face episodes of intermittent hypoxia and it affects men and women. Patients with OSA present hypertension and sympathetic overactivity among several other dysfunctions. Therefore, one important question remains: are the autonomic dysfunctions associated with OSA similar in male and female? This is an unresolved question since sex factors are overlooked in most clinical and experimental studies. Epidemiological data indicate that sex exerts an important influence in the prevalence of OSA and associated comorbidities, such as hypertension. Sex hormones, genetic and neural factors probably are the main players underlying sex differences in the pathophysiology of OSA but they are not yet fully understood. We are using chronic intermittent hypoxia (CIH) as an experimental model of intermittent hypoxia such as those observed in OSA patients to investigate the cardiovascular, sympathetic and respiratory responses in female rats. Our recent studies show that adult and juvenile female rats exposed to CIH develop hypertension similar to age-matched CIH-male rats. Although both males and females develop hypertension after CIH, the most remarkable finding was that CIH-female rats develop changes in the respiratory modulation of sympathetic activity different from those observed in CIH-male rats, characterizing sex differences in the respiratory-sympathetic coupling in response to CIH. Specifically, in CIH-female rats, sympathetic overactivity is linked to inspiration while in CIH-male rats it is linked to the late phase of expiration. In this review we discuss the pathophysiological consequences of CIH, focusing in adult and juvenile female rats and how changes in the respiratory-sympathetic coupling may play a key role in CIH-induced sympathetic overactivity and hypertension in both male and female rats.