The major focus of this experiment is to examine the biochemical mechanisms underlying the over-production of urine that results from negative pressure breathing (NPB). We hypothesize that natural conditions of nocturnal NPB, such as obstructive sleep apnea (OSA), elicit the over-production of urine at night observed as nocturia. At present, there have been no studies which have employed NPB as a surrogate for sleep-related breathing disorders to examine the resulting urine over-production, including the relationship of urine sodium levels and the level of natriuretic peptides in urine. The experimental procedure is designed to elicit these same hemodynamic and renal effects. Associated with the predicted increase in urine volume there will be a comparable increase in urine sodium levels as well as increased levels of natriuretic peptides in urine. To test this hypothesis, we are proposing to monitor urine output and natriuretic peptide excretion in blood and urine using mild negative pressure under highly controlled experimental conditions. Twenty health male and female adults will be recruited to participate in a 220-minute repeated-measures experiment, which includes 80 minutes of breathing against an air pressure of ? 12cm/H2O while in a recumbent position. Urine specimens for urine sodium, osmolality, and natriuretic peptides will be collected at the beginning of the experiment and after every 20-minute period (12 specimens) via urinary catheter. Serum specimens (9 specimens) for natriuretic peptides will be collected at the beginning of the experiment (Time 0) during the interval when negative breathing pressure is applied (Time 5-9) and during the recovery period (Time 10-12). Strict procedures to control for posture, hydration, sodium intake, and caffeine intake are included in the design. Multiple regression analysis will be used to compare differences in the dependent variables across observations with and without negative pressure breathing using subjects as their own controls.
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