The career development plan for this award will consist of two components: A research project and a didactic program. The research project aims to characterize the function of peripheral chemoreceptors and their relation to the sympathetic nervous system (SNS) and blood pressure (BP) in hypertensive patients with obstructive sleep apnea (OSA). Previous work has suggested that apneic hypertensives have high tonic chemoreceptor activity, and depressed chemoreceptor sensitivity. The project's hypothesis is that high tonic chemoreceptor activity contributes to the development of maintenance of hypertension and high SNS tone in OSA patients. To test this hypothesis it is necessary to study four groups of patients: hypertensives and normotensives , with and without sleep apnea. The specific goals of this randomized double blind cross over study include 1) Characterization of tonic chemoreceptor activity by measuring ventilation at room air and during chemoreceptor blockade with 100% O2. 2) Characterization of chemoreceptor sensitivity by measuring ventilation during hypoxia. 3) Characterization of SNS activity at baseline and its response to chemoreceptor blockade or stimulation. 4) Determination of the effect of 7 days nocturnal supplemental O2 on BP, SNS, and chemoreceptor function. If the hypothesis is correct, that high tonic chemoreceptor activity is associated with hypertension and high SNS activity in OSA patients, then treatment with supplemental oxygen may decrease BP and normalize SNS function. A short term implication is that patients with mild to moderate OSA unable to tolerate continuous posit8ive airway pressure, may benefit from nocturnal O2 alone. The didactic program will supplement the clinical research training background of the applicant. The program includes courses in epidemiology, biostatistics, and sleep medicine. Further didactic instruction will include courses and symposia on advanced statistics, clinical trials design and ethical conduct of clinical research. This training will provide the basis of an MPH degree and a solid theoretical background for future conduct of quality clinical research.
