Brain Mechanisms Regulating Sympathetic Vasomotor Function in a Rodent Model of Sleep Apnoea: Neurotransmitters, Networks, and the Circulation

Abstract

Central motor command from the sympathetic networks of the brain and the spinal cord are crucial for maintaining normal cardiovascular function. Understanding the mechanisms that increase sympathetic tone and reflex function are important to prevent neurogenically-mediated hypertension. Chapter 4 investigates the contribution of a hypothalamic neurotransmitter, orexin-A, in causing sympathoexcitation following intermittent hypoxia. Spinal orexin receptor signalling does not contribute to the elevation in sympathetic drive that is observable following intermittent hypoxia but contributes to enhanced chemoreflex sensitivity. Chapter 5 examines the relevance of angiotensin II in eliciting changes in sympathetic activity following intermittent hypoxia. The activation of angiotensin receptors at the level of the subfornical organ and carotid bodies is critical to sympathoexcitation induced by repeated hypoxia. Furthermore, central cardiorespiratory coupling and sensitisation of chemoreflex function are angiotensin II-mediated, and responses that are specific to the carotid bodies. Chapter 6 expands on the previous chapter, demonstrating that the activation of subfornical organ neurons by hypoxia requires central angiotensin receptor signalling. Hypoxia reduces renal blood flow, while simultaneously activating neurons in the subfornical organs. Activation of subfornical organ neurons, at least in some subpopulations, rely on angiotensin type 1 receptor activation. Together, this thesis reports 1) the hypothalamic orexin network contributes to reflex mechanisms of sympathetic regulation, at least during episodic reductions in blood oxygen levels, and 2) angiotensin II is critical for triggering mechanisms that produce sympathoexcitation following intermittent hypoxia, an effect relayed via activation of the subfornical organ and possibly by AT1R-mediated activation of the carotid bodies.