RESUMO
Heart failure (HF) is a prevalent disease in elderly population. Potentiation of the ventilatory chemoreflex drive plays a pivotal role in disease progression, at least in part, through their contribution to the generation/maintenance of breathing disorders. Peripheral and central chemoreflexes are mainly regulated by carotid body (CB) and the retrotrapezoid nuclei (RTN), respectively. Recent evidence showed an enhanced central chemoreflex drive in rats with nonischemic HF along with breathing disorders. Importantly, increase activity from RTN chemoreceptors contribute to the potentiation of central chemoreflex response to hypercapnia. The precise mechanism driving RTN potentiation in HF is still elusive. Since interdependency of RTN and CB chemoreceptors has been described, we hypothesized that CB afferent activity is required to increase RTN chemosensitivity in the setting of HF. Accordingly, we studied central/peripheral chemoreflex drive and breathing disorders in HF rats with and without functional CBs (CB denervation). We found that CB afferent activity was required to increase central chemoreflex drive in HF. Indeed, CB denervation restored normal central chemoreflex drive and reduced the incidence of apneas by twofold. Our results support the notion that CB afferent activity plays an important role in central chemoreflex potentiation in rats with HF.
Assuntos
Corpo Carotídeo , Insuficiência Cardíaca , Idoso , Ratos , Humanos , Animais , Células Quimiorreceptoras/fisiologia , Corpo Carotídeo/fisiologia , Fenômenos Fisiológicos Respiratórios , HipercapniaRESUMO
Carotid bodies (CBs) are main peripheral chemoreceptors involved in breathing regulation. Despite the well-known role played by CBs on breathing control, the precise contribution of CBs on the regulation of lung mechanics remains controversial. Accordingly, we study changes in lung mechanics in normoxia (FiO2 21%) and hypoxia (FiO2 8%) in mice with or without functional CBs. For this, we used adult male mice that underwent sham or CB denervation (CBD) surgery. Compared to sham-operated mice, we found that CBD induced an increase in lung resistance (RL) while breathing normoxic air (sham vs. CBD, p < 0.05). Importantly, changes in RL were accompanied by an approximately threefold reduction in dynamic compliance (Cdyn). Additionally, end-expiratory work (EEW) was increased in normoxia in the CBD group. Contrarily, we found that CBD has no effect on lung mechanics during hypoxic stimulation. Indeed, RL, Cdyn, and EEW values in CBD mice were undistinguishable from the ones obtained in sham mice. Finally, we found that CBD induces lung parenchyma morphological alterations characterized by reduced alveoli space. Together our results showed that CBD progressively increases lung resistance at normoxic conditions and suggest that CB tonic afferent discharges are needed for the proper regulation of lung mechanics at rest.
Assuntos
Corpo Carotídeo , Masculino , Animais , Camundongos , Corpo Carotídeo/fisiologia , Pulmão , Células Quimiorreceptoras/fisiologia , Hipóxia , Respiração , DenervaçãoRESUMO
Unilateral carotid body denervation has been proposed as treatment for sympathetic-related human diseases such as systolic heart failure, hypertension, obstructive sleep apnea, and cardiometabolic diseases. The long-term therapeutic effects of carotid body removal will be maintained if the remnant "buffer nerves," that is, the contralateral carotid nerve and the aortic nerves that innervate second-order neurons at the solitary tract nuclei (NTS), do not modify their contributions to the cardiovascular chemoreflexes. Here, we studied the cardiovascular chemoreflexes 1 mo after unilateral carotid body denervation either by excision of the petrosal ganglion (petrosal ganglionectomy, which eliminates central carotid afferents) or exeresis of a segment of one carotid nerve (carotid neurectomy, which preserves central afferents). Cardiovascular chemoreflexes were induced by intravenous (iv) injections of sodium cyanide in pentobarbitone-anesthetized adult cats. After 1 mo of unilateral petrosal ganglionectomy, without significant changes in basal arterial pressure, the contribution of the contralateral carotid nerve to the chemoreflex increases in arterial pressure was enhanced without changes in the contribution provided by the aortic nerves. By contrast, after 1 mo of unilateral carotid neurectomy, the contribution of remnant buffer nerves to cardiovascular chemoreflexes remained unmodified. These results indicate that a carotid nerve interruption involving denervation of second-order chemosensory neurons at the NTS will trigger cardiovascular chemoreflex plasticity on the contralateral carotid pathway. Then, unilateral carotid body denervation as therapeutic tool should consider the maintenance of the integrity of carotid central chemoafferents to prevent plasticity on remnant buffer nerves.NEW & NOTEWORTHY Unilateral carotid body denervation has been proposed as treatment for sympathetic hyperactivity-related human disorders. Its therapeutic effectiveness for maintaining a persistent decrease in the sympathetic outflow activity will depend on the absence of compensatory chemoreflex plasticity in the remnant carotid and aortic afferents. Here, we suggest that the integrity of central afferents after carotid body denervation is essential to prevent the emergence of plastic functional changes on the contralateral "intact" carotid nerve.