Cardiovascular Regulation in Obstructive Sleep Apnea

Abstract

The majority of patients with obstructive sleep apnea (OSA) suffer from hypertension as a complication of both the metabolic syndrome and OSA. In animal studies, intermittent hypoxia that simulates changes seen in OSA leads to chemoreceptor and chromaffin cell stimulation of sympathetic nerve activity, endothelial damage and impaired blood pressure modulation. Human studies reveal activation of sympathetic nerves, endothelial damage and exaggerated pressor responses to sympathetic neurotransmitters and endothelin. Although treatment of the OSA normalizes sympathetic nerve responses, it only lowers blood pressure modestly. Agents that block the consequences of sympathetic over activity, such as β1 blockers and angiotensin antagonists have effectively lowered blood pressure. Diuretics have been less successful. Treatment of hypertensive patients with OSA usually requires consideration of both increased sympathetic nerve activity and the metabolic syndrome.

Most patients with obstructive sleep apnea (OSA) and hypertension also have multiple aspects of the metabolic syndrome such as insulin resistance, obesity and hyperlipidemia, which lead to atherosclerosis. Pathways leading to hypertension from the intermittent hypoxia of OSA are shown in the upper part of the figure. Pathways leading to hypertension from the metabolic syndrome are shown ascending from the bottom. Both OSA and the metabolic syndrome are associated with endothelial damage. The + signs indicates an exaggerated pressor response to endothelin and to sympathetic agonists in OSA. Excess activation of the renin-angiotensin-aldosterone pathway has been documented in severe human OSA, but not in mild to moderate OSA. Chromaffin cell activation has been demonstrated in animal models of OSA, but not in human subjects. Animal models demonstrate the effects of intermittent hypoxia for most of the descending pathways in the figure. However, the metabolic syndrome is so prevalent in hypertensive humans with OSA that the effects of OSA in humans have not been clearly separated from the effects of the metabolic syndrome.