Vascular Effects of Intermittent Hypoxia

Abstract

Obstructive sleep apnea is characterized by repeated upper airway obstruction during sleep and affects between 5% and 20% of the population. Epidemiological studies reveal that sleep apnea and associated intermittent hypoxemia increase the risk for hypertension and vascular disease but the mechanisms underlying these effects are incompletely understood. This review reports the results of rodent models of intermittent hypoxia (IH) and relates them to the observed hemodynamic and vascular consequences of sleep apnea. These animal studies have demonstrated that IH exposure in the absence of any other comorbidity causes hypertension, endothelial dysfunction, and augmented constrictor sensitivity, all due at least in part to increased vascular oxidative stress. Animal studies have used a variety of exposure paradigms to study intermittent hypoxia and these different exposure protocols can cause hypocapnia or hypercapnia—or maintain eucapnia—with accompanying alterations in plasma pH. It appears that these different profiles of arterial blood gases can lead to divergent results but the impact of these differences is still being investigated. Overall, the studies in rodents have clearly demonstrated that the vascular and hemodynamic impact of intermittent hypoxia provides a strong rationale for treating clinical sleep apnea to prevent the resulting cardiovascular morbidity and mortality.

Inflammation in sleep apnea: An update

“…It has been suggested that the IH of OSA is more inflammatory than stable hypoxia, since cycles of hypoxia and reoxygenation bear a resemblance to ischemia-reperfusion injury which is well known to promote significant oxidative stress [31, 113, 114]. IH-induced inflammation in adipose tissues was examined in vitro by Taylor et al , who exposed primary human subcutaneous and visceral adipocytes to acute IH.…”

Chronic intermittent hypoxia increases sympathetic control of blood pressure: role of neuronal activity in the hypothalamic paraventricular nucleus

“…Whereas maintenance of CIH-induced hypertension is generally agreed to depend on increased systemic vascular resistance, the underlying mechanisms are complex and involve changes in vascular reactivity (1,(22)(23)(24)47) as well as chronically elevated sympathetic nerve activity (SNA) (16,32,60). The latter has been strongly linked to sensitization of the arterial chemoreflex (15,32,45,50,67), which results in tonic activation of sympathetic outflow even at normoxic arterial PO 2 .…”

Cardiovascular Consequences of Sleep Apnea

“…There is a strong association between sleep apnea and hypertension, ischemic heart disease, stroke, arrhythmia, chronic heart failure, and other cardiovascular morbidity and mortality [6,7]. Patients with sleep apnea who do not have overt cardiovascular disease can have subclinical structural and functional changes marking atherosclerosis [8] and endothelial dysfunction [9], suggesting the primary role of these processes in the development of cardiovascular morbidity.…”

“…In another study, hypocapnic (but not eucapnic) intermittent hypoxia caused more profound increases in right ventricular mass [156]. It is likely that CO 2 interferes with the development of pulmonary hypertension and modulates the pulmonary responses to hypoxia in rats exposed to chronic hypoxia [7]. Despite these differences and markedly divergent changes in arterial blood gases, the rodent model of intermittent hypoxia continues to provide good opportunities to study the mechanisms of cardiovascular comorbidity of sleep apnea.…”