THE ASSOCIATION OF RACE AND SEX TO THE PRESSURE NATRIURESIS RESPONSE TO STRESS Gregory A. Harshfield, PhD; Coral Hanevold, MD; Gaston K. Kapuku, MD, PhD; Yanbin Dong, MD, PhD; Martha E. Castles, MA; David A. Ludwig, PhD Objective: Sympathetic nervous system acti- vation promoting sodium retention has long been recognized to play a significant role in the development and maintenance of salt- sensitive hypertension. The purpose of this study was to examine the influence of race and sex on the pressure natriuresis response to prolonged behavioral stress in youth. Methods: The 190 subjects included 94 boys (41 African American, 53 Caucasian) and 96 girls (44 African American, 52 Caucasian) of similar age (17–19 years). The stress test was composed of a one hour competitive video game task preceded and followed by two-hour rest periods. Blood pressure (BP) was obtained at 15 minute intervals and sodium excretion (U Na V) was measured hourly. The general linear model was used to model the effects of race, sex, and their interaction on the variables of interest. Results: Caucasians, compared to African Americans, had a greater change in U Na V (F[1,183]55.28, P5.0227), as did boys com- pared to girls (F[1,183]55.72, P5.0178), with no interaction between race and sex. The race-by-sex interaction was significant for the change in systolic BP (F[1,183]55.66, P5.0184), with Caucasian girls showing a smal- ler change than the other three race/sex groups. Conclusion: African Americans have a reduced natriuretic response to stress, which may be a marker or mechanism for the development of salt-sensitive hypertension in this popula- tion. The race difference within girls is of interest and requires further investigation. (Ethn Dis. 2007;17:498–502) Key Words: Stress, Sodium, Blood Pressure, Natriuresis, Hypertension, Race, Sex INTRODUCTION It is well-established that African Americans compared to Caucasians have a greater incidence and prevalence of essential hypertension (HTN). 1–4 Studies, which reported changes in blood pressure (BP) in response to changes in sodium intake (ie, salt sensitivity), demonstrated that impaired sodium regulation in African Americans contributes to this difference. 3,5–7 We 8,9 and others 10–12 hypothesized that an impaired natriuretic response to behavioral/mental stress (ie, im- paired stress-induced pressure natriure- sis [SIPN]) is a potential mechanism through which impaired sodium regu- lation contributes to the increased prevalence of HTN in African Amer- icans. Impaired SIPN differs from the traditional assessment of salt sensitivity in that the load is ‘‘delivered’’ by the increase in renal sympathetic nerve activity resulting from the stress rather than by a diet or infusion. Three lines of research support this hypothesis and include: 1) studies that demonstrated an important role of the sympathetic nervous system (SNS) in the develop- ment of salt-sensitive HTN 13–17 ; 2) animal studies that demonstrated be- haviorally induced SNS activation results in salt-sensitive HTN by in- ducing sodium retention, which in- creases intravascular volume and there- fore cardiac output and BP 15,18,19 ; and 3) previous data by Light 10 on a small sample of adults (14 African Ameri- can, 14 Caucasian), and our group 9 , in youth. Therefore, the purpose of this study was to confirm the race difference in SIPN and examine potential interactions between race and sex. METHOD Study Population The volunteer sample consisted of 190 unrelated subjects and included 94 boys (41 African American, 53 Cauca- sian) and 96 girls (44 African American, 52 Caucasian) of similar age (17– 19 years) who participated in two separate studies (ie, two cohorts) that employed the same protocol. The studies were approved by the Human Assurance Committee of the Medical College of Georgia. Written informed consent (for those $18 years of age) or parental consent and subject assent (for those ,18 years of age) was obtained prior to testing. Table 1 provides the subject’s baseline characteristics by race and sex for the outcome variables evaluated in this study. The subjects were all normotensive, healthy, not on any over-the-counter or prescription medications (except for acne), and without a history of any medical di- agnosis. They were recruited from area schools and by word-of-mouth. Protocol Our protocol has been described in detail previously. 9,20 Briefly, the sub- jects were placed on a controlled sodium From the Georgia Prevention Institute (GAH, GKK, YD, MEC, DAL), and the Departments of Pediatrics (GAH, CH, GKK, YD, MEC, DAL), Biostatistics (DAL) and Physiology (GAH), Medical College of Georgia; Augusta, Georgia. Address correspondence and reprint requests to Gregory A. Harshfield, PhD; Georgia Prevention Institute; Medical Col- lege of Georgia; MCG Annex H.S. 1640, Augusta, GA 30912-4534; 706-721-1755; 706-721-7150 (fax); Gharshfi@mail.mcg. edu The purpose of this study was to confirm the race difference in SIPN and examine potential interactions between race and sex. 498 Ethnicity & Disease, Volume 17, Summer 2007