Effect of episodic hypoxia on sympathetic activity and blood pressure
Introduction
Repetitive obstructive sleep apnea (OSA) in humans as well as animals results in elevation of systemic blood pressure (BP) with each apnea as well as a more prolonged elevation extend beyond the period of apneas (Shepard, 1985). This, along with epidemiologic data, supports the hypothesis that repetitive airway obstructive with desaturation can lead to secondary hypertension. Indeed, snoring and repetitive sleep apnea may be major causes of hypertension in patients previously labeled with essential hypertension.
Animal preparations of acute apnea in the dog, pig, and lamb have provided the opportunity to study in depth, acute hemodynamic and cardiovascular response to apnea (Kimoff et al., 1994, Brooks et al., 1997). But it may take many years for nightly, repetitive apnea to lead to sustained daytime systemic hypertension, making prospective studies of hypertension in these models or humans difficult or impossible. Currently, the majority of hypertension research is conducted in rodents because of the many similarities of BP control and cardiovascular response between these animals and humans. The technology of knockout and transgenic mice have made rodents even more important in such research. Given the short life span of rodents, many of the models of chronic renal and endocrine hypertension paralleling human clinical disease can be studied in greater depth than is possible in humans. Thus, several groups are now working on animal preparations in which recurrent events during sleep can be induced over a period of weeks or months to test the hypothesis that apnea/hypoxia leads to chronic hypertension. This monograph will discuss the use of an episodic hypoxia rat (EHR) preparation in which rats are exposed to recurrent periods of episodic hypoxia (EH) mimicking the recurrent desaturation of OSA. EH is continued for eight hours per day for 35 days, inducing sustained elevation of BP.
Section snippets
The chronic episodic hypoxia model
We constructed 25 chambers where rodents could be exposed to rapid swings in ambient oxygen concentration (FiO2), inducing changes in oxygen saturation (SaO2) similar to that seen in humans with sleep apnea (Fig. 1). These cylindrical Plexiglas chambers are 28 cm in length with a diameter 10 cm and volume of 2.4 L. The ends are covered with a snug fitting lid in which holes are drilled that can be plugged with perforated rubber stoppers. A timed solenoid valve distributes pure nitrogen to each
Plasma renin in the EHR
Plasma renin activity (PRA) is regulated by sympathetic nerves and can affect diurnal BP through the renin–angiotensin system. Thus, PRA could be instrumental in chronic BP elevation in the EHR. To this end PRA was examined in 24 Sprague Dawley rats after 35 days of EH. Half of the group was treated with losartan [an angiotensin 1 (AT1) receptor blocker] 15 mg/kg per day by gastric gavage. The other half were treated with vehicle (Fletcher et al., 1999). The groups were divided as follows: five
Uncited references
Bao and Fletcher, 1997, Fletcher et al., 1999.
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