Obstructive sleep apnea is a disorder known to be associated with increased cardiovascular mortality and morbidity. Part of this association is undoubtedly due to the occurrence of hypertension both in association with apneic events and during the day in these patients. Evidence is accumulating that the association between sleep apnea and hypertension is in fact causal. There are currently a number of hypotheses regarding the mechanisms responsible for acute elevations in blood pressure at night and for sustained elevations of blood pressure in the day in patients with sleep apnea. However, due to the difficulty in controlling experimental conditions in clinical situations, and the multiplicity of inputs, much of the current knowledge remains speculative. The investigator and his colleagues have developed a chronic dog model of sleep apnea. Using this model and an acute cat preparation where indicated, the investigator proposes an integrated series of studies dissecting out the multiplicity of possible inputs to the regulation of blood pressure. The proposal is geared to a number of specific aims.
Specific Aim 1 is to study how input from chemoreceptors and pulmonary afferents act to increase blood pressure during the intra-apneic period.
Specific Aim 2 will be to examine those factors responsible for the immediate post-apneic increase in blood pressure, especially the role of post apneic arousal and hyperventilation.
Specific Aim 3 will examine the mechanisms by which repetitive apneas lead to elevations of blood pressure during the day. Specifically the role of sleep fragmentation and periodic stimulation of chemoreceptors will be examined. A number of specific and relevant hypotheses are to be tested for each aim. Both the afferent and efferent limbs of the response to various stimuli will be examined.
