Effects of A2a Receptors on the Hypoxic Ventilatory Response in Rats Exposed to Chronic Sustained Hypoxia

BAŞARAN K. E., Moya E., Fu Z., Powell F. L.

Experimental Biology 2015, Boston, United States Of America, 28 March - 01 April 2015, vol.29, no.1, pp.29, (Full Text)

  • Publication Type: Conference Paper / Full Text
  • Volume: 29
  • City: Boston
  • Country: United States Of America
  • Page Numbers: pp.29
  • Erciyes University Affiliated: Yes

Abstract

Recent studies show that long term facilitation of phrenic nerve activity (LTF) with acute intermittent hypoxia (IH) involves two signaling pathways. In addition to the well-known serotonergic (Gq) pathway, a Gs pathway can be activated by adenosine receptor 2 (A2a) agonists and cause LTF without IH (J Neurosci 28:2033-42, 2008). Gs can inhibit the Gq pathway as A2a antagonists increase LTF from IH by disinhibiting Gq (J Physiol 588:255-66, 2010). We tested the hypothesis that Gs also contributes to plasticity in ventilatory control during chronic sustained hypoxia (CH) by measuring the effects of A2a antagonists and agonists on ventilatory responses to hypoxia and hypercapnia in adult male rats before and after one week of CH (PO2 = 80 Torr in a hypobaric chamber). Ventilation measured in awake unrestrained rats with barometric pressure plethysmography increased after CH; acute ventilatory responses to hypoxia or hypercapnia increased also. Acute administration of A2a antagonist (MSX-3, 1 mg/Kg i.p.) after CH did not change ventilation or acute ventilatory responses. A2a agonists (CGS 21680, 100 µg/Kg i.p.) before CH had no effect on ventilation or ventilatory responses, in contrast to stimulation reported for sleeping rats (J Neurosci 28:2033-42, 2008). The results do not support a role for Gs in the increased ventilatory drive and hypoxic responses with CH, in contrast to their role in LTF in IH.  

Supported by NIH RO1 HL-081823.