Chronic intermittent hypoxia augments sympatho-excitatory response to ATP but not to l-glutamate in the RVLM of rats

Daniel B. Zoccal, J. Pablo Huidobro-Toro b, Benedito H. Machado a, 

Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil,

Nucleotide Research Lab, Department of Physiology, Faculty of Biological Sciences, P. Catholic University, Santiago, Chile 

Chemoreceptors located in the carotid bodies sense oxygen levels in the blood and are able to make respiratory and cardiovascular adjustments by activating neuronal mechanisms. When there is an increase in the activation of these chemoreceptors it can lead to the development of cardiovascular and respiratory pathological conditions. In this article, they were interested in obstructive sleep apnea (OSA), many of us already know that OSA can lead to the development of hypertension. Individuals that suffer from OSA experience chronic intermittent hypoxia (CIH is basically alteration between low and ambient air conditions). As we already know, glutamate is major neurotransmitter it has been shown that Glu release in the VLM cause excitation of pre-sympathetic and respiratory neurons. ATP may also play a role in this too. So the authors wanted to see whether CIH modulated the expression of Glutamatergic (Glu) and purinergic (ATP) receptors. They used microinjection and western blot techniques, in order to investigate their question. The investigators in this article were specifically interested in Bötzinger complex (Bötc) area. Bötc is important for respiratory control. When they were trying to functional identify this area using glutamate, they were looking for increase in sympathetic excitation along with a decrease in phrenic nerve activity.

For the microjection results, they found that there was no difference between the control and the CIH group in the response to glutamate. Then by western blot, they showed that there was no difference in the expression of Glutamatergic receptor protein between the groups. The glutamate receptors that they looked at using western blot were NMDAR1 and GluR2/3. For the purinergic receptors, they looked at using western blot were P2X1, P2X3, P2X4 and P2Y2. In the microinjection experiments, they found that there was a greater response to ATP in the CIH compared to the control suggesting that there is a possible up regulation of purinergic receptors due to CIH. The western blot results showed that there was increase in P2X3 and P2X4 protein in the CIH compared to control, which further supports their data. In CIH, there is increased SNA in these individuals. This article shows a possible factor that may contribute to the increase in SNA may be mediated by increased P2X3 and P2X4 in the VLM.