Effects of chronic intermittent hypoxia on purinergic transmission in the carotid bodies of rats

Abstract

The Carotid bodies (CBs) are the main O2 sensors in rats, because it contains cells highly sensitive to reductions in the O2 partial pressure in the arterial blood (hypoxia). During hypoxic conditions, the CBs release neurotransmitters, mainly from the purines family (ATP and adenosine), which act on its metabotropic (P2Y1, P2Y2, A2A, A2B, A1 and A3) and ionotropic (P2X3 and P2X2) receptors, contributing to the cardiovascular, mediated by sympathetic/parasympathetic autonomic nervous system (increases in arterial pressure and bradycardia, respectively) and respiratory responses (pulmonary hyperventilation). The ATP and adenosine levels are modulated by ectonucleotidases [(Ectonucleoside triphosphate diphosphohydrolase: E-NTPDases) (ecto-5'-nucleotidase: E5'Nt)], present in the plasmatic membrane and in the intracellular compartments of CBs cells, resulting in the adenosine production. Chronic intermittent hypoxia (CIH) increases the tonicity and chemosensory response of CBs from rats, contributing to the sympathetic overactivity and arterial hypertension observed in this experimental model. However, the contribution of purinergic transmission to these changes in the CBs in response to CIH remains unknown. Therefore, the hypothesis of this Research Project is: CIH increases the purinergic transmission (ATP and adenosine) in the CBs, contributing to it tonicity and hyperreflexia to hypoxia in rats. We will evaluate the changes in the purinergic transmission induced by CIH (10 days) in the CBs, analyzing the expression of ATP and adenosine ionotropic and metabotropic receptors, as well as the expression of E-NTPDase and E5'Nt in CBs from rats. We will also record the carotid sinus nerve activity to evaluate the contribution of purinergic transmission to the increase of tonicity and reflex response to hypoxia of the CBs from rats submitted to CIH. The understanding of these mechanisms could contribute to the development of new therapeutic approaches in pathologies associated with increases of CBs tonicity, such as neurogenic hypertension, heart failure and obstructive sleep apnea.