One of the major manifestations of obstructive sleep apnea (OSA) is profound and repeated (episodic) hypoxia during sleep. Acute hypoxia leads to stimulation of the peripheral chemoreceptors, which in turn directly increase sympathetic outflow. It is believed that this increase in sympathetic outflow is directly responsible, at least in part, for the acute blood pressure (BP) changes seen in OSA. It is difficult however, to study the chronic effects of repeated episodic hypoxia (EH) in humans since the chronic cardiovascular changes may take many years to manifest. For this reason, we developed a method of providing recurrent short periods of hypoxia (resembling the episodic desaturation in humans with OSA) to rats for 35 days, stimulating the chemoreceptors and the sympathetic nervous system, allowing examination of the chronic cardiovascular response to EH. The result of EH in rats is a 10-14 mmHg increase in resting (unstimulated) mean BP that lasts for several weeks after cessation of the daily EH. This BP increase is blocked by carotid body denervation, sympathetic nerve ablation, renal sympathectomy, adrenal medullectomy, and the angiotensin-1 receptor blocker losartan. Thus, it appears that adrenergic and renin-angiotensin system over-activity contribute to the early chronic elevated BP in EH and perhaps in human hypertension associated with OSA.