Possible Breathing Influences on the Control of Arterial Pressure After Sino-aortic Denervation in Rats.

PURPOSE OF REVIEW: Surgical removal of the baroreceptor afferents [sino-aortic denervation (SAD)] leads to a lack of inhibitory feedback to sympathetic outflow, which in turn is expected to result in a large increase in mean arterial pressure (MAP). However, few days after surgery, the sympathetic nerve activity (SNA) and MAP of SAD rats return to a range similar to that observed in control rats. In this review, we present experimental evidence suggesting that breathing contributes to control of SNA and MAP following SAD.The purpose of this review was to discuss studies exploring SNA and MAP regulation in SAD rats, highlighting the possible role of breathing in the neural mechanisms of this modulation of SNA. RECENT FINDINGS: Recent studies show that baroreceptor afferent stimulation or removal (SAD) results in changes in the respiratory pattern. Changes in the neural respiratory network and in the respiratory pattern must be considered among mechanisms involved in the modulation of the MAP after SAD.

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

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.

Inspiratory modulation of sympathetic activity is increased in female rats exposed to chronic intermittent hypoxia.

NEW FINDINGS: What is the central question of the study? There are sex differences in the respiratory network and in the regulation of arterial blood pressure. Female rats develop hypertension after chronic intermittent hypoxia (CIH). In this context, we evaluated the respiratory-related mechanism underlying the development of hypertension in CIH-exposed female rats. What is the main finding and its importance? Female rats exposed to CIH develop changes in the respiratory pattern related to inspiration and sympathetic overactivity phase locked to the inspiratory phase of the respiratory cycle, which is different from CIH-exposed male rats. These data suggest a specific respiratory mechanism for sympathetic overactivity in hypertensive CIH-exposed female rats. Chronic intermittent hypoxia (CIH) induces sympathetic overactivity and hypertension in male rats. Enhanced respiratory modulation of sympathetic activity in juvenile male rats exposed to CIH occurs in the expiratory phase of the respiratory cycle, characterizing changes in respiratory-sympathetic coupling. Different from other experimental models of hypertension, CIH induces an increase in arterial pressure in adult female rats similar to that observed in male rats. However, the mechanisms underlying the hypertensive phenotype in CIH-exposed female rats remain to be elucidated. Moreover, several lines of evidence have documented sex differences in respiratory network activity in response to hypoxia. Considering that CIH-exposed male rats present an increase in the respiratory modulation of sympathetic activity and there are sex differences in the respiratory network, we hypothesized that CIH-exposed female rats develop an increase in the respiratory modulation of sympathetic activity different from CIH-exposed male rats. In this study, we investigated sympathetic and respiratory activities in juvenile female rats exposed to CIH using an in situ working heart-brainstem preparation. The CIH-exposed female rats developed changes in the respiratory pattern and changes in the respiratory-sympathetic coupling marked by sympathetic overactivity phase locked to inspiration, which was different from male rats exposed to CIH. This study revealed a specific respiratory-related mechanism for sympathetic overactivity linked to inspiration that explains, at least in part, the hypertensive phenotype in female rats exposed to CIH.

Cardiovascular and respiratory responses to chronic intermittent hypoxia in adult female rats.

NEW FINDINGS: What is the central question of this study? Chronic intermittent hypoxia (CIH) induces hypertension in male rats. There is evidence that the development of high blood pressure in females is attenuated in other models of hypertension. Due to the lack of information about the cardiovascular effect of CIH in female rats, we set out to determine whether female rats develop hypertension after CIH. What is the main finding and its importance? Different from other experimental models of hypertension, adult female rats develop high blood pressure after CIH. These findings provide new perspectives for a better understanding of the neural mechanisms underlying the development of hypertension in females. Adult male rats develop hypertension in response to chronic intermittent hypoxia (CIH). Female rats are known to be protected against the development of hypertension in several experimental models. In this study, we aimed to verify whether the development of hypertension was also prevented in female rats exposed to CIH. Adult female rats were submitted to 35 days of CIH, 8 h per day. At the end of the CIH protocol, the rats were anaesthetized for the implantation of an arterial catheter and the next day the mean arterial pressure and heart rate were recorded in conscious rats. Considering that changes in the respiratory pattern have been associated with the development of hypertension in the CIH model, the respiratory pattern of adult female rats was also evaluated after CIH exposure using whole-body plethysmography. Adult female rats submitted to CIH (n = 27) presented a significant increase in mean arterial pressure when compared with the control group (n = 26). Moreover, CIH-exposed female rats presented an increase in the frequency and duration of apnoeas when compared with control rats. These data show that adult female rats develop changes in the respiratory pattern and high blood pressure in response to CIH.