Obstructive sleep apnea (OSA) is a highly prevalent disorder characterized by recurrent upper airway obstruction during sleep. These episodes are terminated by arousals and are commonly associated with hypoxemia. The acute hemodynamic and autonomic perturbations that accompany obstructive apneas can lead to sustained diurnal hypertension. [1][2][3] In a cross-sectional study of a sleep clinic patients 60% of men and women with severe OSA had hypertension. 4 In populationbased prospective studies, patients with severe OSA had three times the risk of developing hypertension within 5 years, independent of other risk factors. 1 Current evidence suggests that sympathoexcitation, inflammatory processes, oxidative stress, and endothelial dysfunction play important roles in the pathogenesis of hypertension and vascular complications in OSA. [5][6][7][8][9] However, the exact mechanisms of hypertension and varying susceptibility to endothelial dysfunction among patients with OSA are not well understood.Endothelial-dependent vasodilatory capacity is primarily regulated by local production of nitric oxide (NO) and modulated by carbon monoxide (CO). 10-12 CO is predominantly released during heme metabolism by heme oxygenase (HO), generating iron and biliverdin. Biliverdin is further metabolized to bilirubin by biliverdin reductase. HO has been reported to be present in all tissues and colocalizes with NO synthase in the vasculature. 13,14 Like NO, the ability of CO to relax blood vessels occurs through soluble guanylate cyclase with increases in guanosine 3′,5′-cyclic monophosphate (cGMP) and activation of calcium-gated potassium channels. 15,16 The activation of potassium channels inhibits calcium entry from
BackgroundObstructive sleep apnea (Osa) is a highly prevalent disorder that increases the risk of systemic hypertension and cardiovascular diseases. Heme oxygenase (HO) has been shown to be upregulated in patients with Osa and its overexpression in mice causes hypertension. End products of HO are carbon monoxide (CO) and bilirubin. CO exerts a pleiotropic action on vasoregulation. Despite high prevalence and incident of hypertension in Osa, its pathophysiology is not well-understood, particularly in regard to varying susceptibility of patients to hypertension. We investigated the role of HO in endothelial dysfunction and hypertension in Osa.