LBPS 01-25 MECHANISMS OF PRESSOR AND BRADYCARDIC RESPONSES TO ACUTE EPISODIC HYPOXIA IN CONSCIOUS RATS

Abstract

Objective: Pronounced pressor and bradyarrhythmic responses are frequently observed in patients with obstructive sleep apnea, and has been recapitulated in rodents subjected to intermittent hypoxia (Fletcher et al., Hypertension, 1992). Some substances such as acetylcholine (ACh) and adenosine are known to cause bradycardia, and have reported to be increased in the myocardium during experimental myocardial ischemia. We therefore tested the hypothesis that the adenosine-signaling, along with ACh signaling are responsible for the pressor and bradycardic responses observed during acute hypoxia. Design and Method: Male Wistar rats (n = 6) previously implanted with telemetry devices to monitor arterial blood pressure (TRM54P, TR-Millar) and heart rate were exposed to either 90-s of episodic hypocapnic (nadir inspired O2 fraction = 5%) or eucapnic (nadir inspired O2 fraction = 5%; peak inspired CO2 fraction = 5%) hypoxia in a sealed chamber. Results: Both acute hypocapnic and eucapnic hypoxia elicited a marked pressor response, followed by significant bradycardia; eucapnic hypoxia evoked greater cardiovascular responses. The observed cardiovascular responses were not mediated solely by the baroreflex, as α1-adrenergic receptor blockade with prazosin (2 mg/kg, ip) suppressed pressor only, but not bradycardic responses during acute hypoxia. Both M2-ACh receptor selective antagonist AF-DX116 (1 mg/kg, ip) and adenosine A1-R selective antagonist DPCPX (2 mg/kg, ip) significantly attenuated non-baroreflex mediated bradycardia. Interestingly, desensitization of TRPV1 expressing neurons by systemic capsaicin treatment (50 mg/kg ip) abolished both pressor and bradycardic responses in hypocapnic hypoxia but not in eucapnic hypoxia. Conclusions: Non-baroreflex mediated bradycardia during acute hypoxic hypoxia is mainly due to stimulations of both adenosine A1 and muscarinic ACh receptors. These signal pathways may play important roles in decelerating heart rate in order to protect heart against ATP depletion followed by cell death during severe tissue hypoxia. TRPV1-expressing neurons also play an important role in these cardiovascular responses as a peripheral O2 sensor during acute hypoxia.