The purpose of this study is to test the hypothesis that blood pressure sensitivity to high sodium intake in healthy humans is characterized by increased urinary excretion of two endogenous sodium pump inhibitors, marinobufagenin (MBG), and ouabain-like compound (OLC). The study also tests the hypothesis that women who breathe slowly and have high resting end tidal CO2 at rest are more likely to have low plasma renin activity and sodium sensitivity of blood pressure than those who breathe more rapidly and maintain lower end tidal CO2.

The experiments will involve a common procedure of sodium restriction followed by sodium loading of normotensive (having normal blood pressure) humans. However, the first experiment will involve continuous urine collection throughout the experimental period in a smaller group of men and women, while the second experiment will involve urine collection only at the end of each diet period in a larger group of normotensive women. If, as expected, experiment one shows that sodium loading produces MBG increases that are sustained throughout the sodium loading period, then experiment two will also be able to address a third issue: that is whether MBG or OLC response to sodium loading is specific to breathing pattern or sodium sensitivity. It is hypothesized that women with inhibited breathing who are sodium sensitive will show higher levels of MBG, even before sodium loading, but also following sodium loading.

Each participant will be seen at the Clinical Research Unit for a screening visit and on days 6 and 12, and consume a low sodium diet for 6 days followed by a high sodium diet for 6 days. Research staff will meet with the participant at regular intervals for meal provision and transfer of 24-hr urine collections (if applicable). Respiration and blood pressure will be measured on the last day of each sodium diet.

Inclusion Criteria:

• Age 40-70
• Caucasian
• Nonsmoking
• Free of respiratory, cardiac, liver and kidney disease, and diabetes
• Resting systolic blood pressure less than or equal to 139 mmHg AND resting diastolic blood pressure of less than or equal to 89 mmHg15
• BMI less than or equal to 30
• Negative pregnancy test for female participants whose last menstrual period was less than one year prior to study enrollment
• For Group 1, willing to provide 24-hr urine samples for 12 consecutive days
• For Group 2, women on combination oral contraceptives (those containing estrogen and progesterone) will be eligible for the study, with equal numbers in the "fast" and "slow" breathing groups
• For Group 2, in premenopausal women, regular menstrual cycles for at least 6 months prior to study entry

Exclusion Criteria:

• Presence of respiratory, cardiac, liver or kidney disease; diabetes, or hypertension
• Use of medications which can affect respiratory rate, such as major tranquilizers, narcotics, or benzodiazepines
• Diuretic or steroid use
• Cigarette smoking within the past 12 months
• BMI > 30 kg/m2
• Postmenopausal women on hormone replacement therapy
• Pregnancy or lactation in the last 12 months
• In premenopausal women, irregular menstrual cycles in the 6 months prior to study entry
• For Group 2, respiratory rate in the middle third of the distribution of breathing frequency in BLSA
• For Group 2, pre-menopausal women not taking oral contraceptives who are in the follicular phase of the menstrual cycle

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