OF WORK. This program is concerned with the role of environmental and behavioral factors in the development of hypertension. An ongoing clinical research project is testing the hypothesis that blood pressure sensitivity to high sodium intake in healthy women is potentiated by an inhibited breathing pattern. It is based on previous research which found that (a) high sodium intake elevates blood pressure of large animals while under behavioral stress that inhibits respiration, and (b) chronic perceived stress in women is accompanied by mild hypoventilatory breathing at rest. Related studies in this program also found that breath holding increases plasma and urinary concentrations of an endogenous sodium pump inhibitor (marinobufagenin) that has been implicated in human hypertension. Therefore, the present study also addresses the effects of low and high sodium diet on circulating marinobufagenin. During the past year, thirty four women have been evaluated for eligibility for inclusion in the study of the effects of low and high sodium diet on blood pressure and marinobufagenin. Each eligible subject is provided with nutritionally balanced meals to control for low and high sodium intake during two successive six-day intervals. Enteric-coated sodium chloride capsules, prorated for body weight, supplement the high sodium diet. Physiological and biochemical adaptations of each participant are monitored during each of three 20 min sessions of seated rest before and after the low and high sodium diets. Breathing is monitored during these sessions via a new technology, the Lifeshirt, which provides frequency, tidal volume, minute ventilation and other respiratory measures from an expandable vest attached to a portable recorder. End tidal CO2 is monitored via a nasal cannula connected to a respiratory gas monitor. Systolic and diastolic blood pressure are recorded at six min intervals during the clinic sessions. In addition, 24 hr blood pressure is monitored at the end of the low and high sodium diet periods. Blood samples are obtained to evaluate circulating levels of sodium and marinobufagenin. Salivary samples are obtained daily to assess possible changes in pH. Finally, 24-hr urine samples are obtained at the end of the low and high sodium dietary periods for analysis of dietary compliance and marinobufagenin excretion. In a subset of male and female subjects, 24 hr urine samples are obtained for each of the 12 experimental days. To date, the experiment has been completed with 19 women and one man. Median individual differences in breathing frequencies ranged from 10 to 18 breaths per minute. Changes in systolic blood pressure have ranged from -2 to +13 mmHg. Preliminary analysis indicates an inverse correlation of -.54 between individual breathing frequency and diet-induced change in systolic blood pressure. The study remains in progress, but confirmation of the hypothesis would provide new insights into the pathways by which stress can contribute to the development of high blood pressure, and set the stage for interventions designed to ameliorate sodium sensitivity of blood pressure and its role in the pathogenesis of some forms of hypertension.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Intramural Research (Z01)
Project #
1Z01AG000600-16
Application #
6969304
Study Section
(CS)
Project Start
Project End
Budget Start
Budget End
Support Year
16
Fiscal Year
2004
Total Cost
Indirect Cost
Name
Aging
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Anderson, David E; Parsons, Beverly A; McNeely, Jessica C et al. (2007) Salt sensitivity of blood pressure is accompanied by slow respiratory rate: results of a clinical feeding study. J Am Soc Hypertens 1:256-263
Scuteri, Angelo; Stuehlinger, Markus C; Cooke, John P et al. (2003) Nitric oxide inhibition as a mechanism for blood pressure increase during salt loading in normotensive postmenopausal women. J Hypertens 21:1339-46
Anderson, D E; Scuteri, A; Metter, E J et al. (2001) Association of high resting end tidal CO2 with carotid artery thickness in women, but not men. J Hypertens 19:459-63
Anderson, D E; Scuteri, A; Agalakova, N et al. (2001) Racial differences in resting end-tidal CO2 and circulating sodium pump inhibitor. Am J Hypertens 14:761-7
Anderson, D E; Parsons, D J; Scuteri, A (1999) End tidal CO2 is an independent determinant of systolic blood pressure in women. J Hypertens 17:1073-80