Repetitive, episodic hypoxia causes diurnal elevation of blood pressure in rats.

Abstract

An association between chronic high blood pressure and obstructive sleep apnea has been described. We hypothesized that repetitive episodic hypoxia patterned after the hypoxia seen in sleep apnea could contribute to diurnal elevation of blood pressure. Using 12-second infusions of nitrogen into daytime sleeping chambers, four groups of male rats (250-375 g) were subjected to intermittent hypoxia (3-5% nadir ambient oxygen) every 30 seconds, 7 hours per day for up to 35 days. In one group, blood pressure was measured weekly by the tail-cuff method in conscious animals during 5 weeks of episodic hypoxia. In the other three groups, blood pressure was measured in conscious animals via femoral artery catheters at baseline and after 20, 30, or 35 days of exposure. Additional groups served as controls: two sham groups housed in identical "hypoxia" chambers received compressed air instead of nitrogen (35 days) while two other groups remained unhandled in their usual cages (35 days). Both groups challenged with 35 days episodic hypoxia showed significant increases in blood pressure compared with controls: the tail-cuff rats showed a 21 mm Hg increase in systolic pressure (/?<0.05) and the intra-arterially measured rats a 13.7 mm Hg increase in mean arterial pressure (p<0.05). The 30-day exposed rats also showed a 5.7 mm Hg increase in mean pressure over baseline (p<0.05). Blood pressure did not change significantly from baseline in the control groups. Left ventricle-to-body weight ratio was higher in both 35-day exposed groups than in unhandled or sham controls. This duration-of-exposure-related blood pressure response to hypoxia along with increased left ventricular size after 35 days indicates that chronic intermittent hypoxia could be a mechanism directly contributing to diurnal arterial blood pressure elevation. 1 Chronic hypertension seen in OSA patients may be reversed by treatment of the apnea.2 -4 Other reports show an increased prevalence of sleep apnea in populations of middle-aged men with primary hypertension, 5 -8 but this association has been challenged by more recent epidemiological studies.910 Possible mechanisms for the development of long-term diurnal blood pressure (BP) elevation in this setting are stress related to episodic repetitive hypoxia, disruption of sleep architecture, and modification of the cardiovascular system (including fluid balance) in response to marked fluctuations in intrathoracic pressure. There have been no studies to date examining the effect of any of these individual mechanisms on long-term diurnal BP. It would be quite difficult to prospectively examine factors effecting diurnal BP in humans since such changes may take many years to manifest in the face of progressively more severe, recurrent OSA. One approach is to develop an animal model with a sufficiently short life span in which some conditions of OSA can be duplicated. We chose the rat as a suitable animal in which to examine the effects of hypoxia on BP because of extensive knowledge about mechanisms of systemic hyperte...

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Intermittent hypoxia degrades HIF-2α via calpains resulting in oxidative stress: Implications for recurrent apnea-induced morbidities

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Chronic intermittent hypoxia predisposes to liver injury

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