Sleep disordered breathing (apnea, hypopnea, and high upper airway resistance) has emerged as an independent risk factor for hypertension. The goal of this project is to determIne the mechanisms by which sleep disordered breathing causes acute and chronic blood pressure elevation in humans. We propose that intermittent asphyxia during sleep raises blood pressure via an increase in sympathetic vasomotor outflow to the peripheral circulation.
Aim l will examine the mechanisms by which exposure to asphyxia causes persistent sympathetic activation which outlasts the chemical stimuli. We hypothesize that hypoxia, acting systemically or at the carotid chemoreceptor, triggers this response.
Aim 2 will investigate the cause of dissociation between sympathetic vasomotor outflow and vascular resistance during exposure to asphyxia. We propose that adenosine, via direct and indirect vasodilator effects, is responsible for this phenomenon.
Aims 3 and 4 will examine mechanisms for neurocirculatory responses to apnea. We hypothesize that the acute pressor response is critically dependent on sympathetic nervous system activation but not on elimination of input from pulmonary stretch receptors.
Aim 5 will determine the effects of long- term nasal continuous airway pressure treatment on blood pressure in individuals with mild to moderate sleep disordered breathing. We expect that our experiments will provide explanations for the sympathetic overactivity and hypertension seen in individuals with sleep disordered breathing and, in turn, lead to a more rational approach to therapy.
