Prehypertensive African-American Women Have Preserved Nitric Oxide and Renal Function but High Cardiovascular Risk

Aims: African-Americans, in particular women, exhibit disproportionate levels of hypertension, inflammation, and oxidative stress compared to other ethnic groups. The relationship between prehypertension, renal function, inflammation, and oxidative stress was examined. Methods: Twenty-eight African-American women (53.5 8 1.1 years) followed an AHA diet and then underwent 24-hour ambulatory BP (ABP) monitoring. Urinary albumin (uAlb), serum and urinary creatinine, glomerular filtration rate (GFR), 24-hour urinary Na + excretion, plasma superoxide dismutase, total antioxidant capacity (TAC), urinary (uNOx) and plasma (pNOx) nitric oxide levels, and high-sensitivity C-reactive protein (hsCRP) were measured. Results: When the group was divided by average 24-hour ABP into optimal and nonoptimal groups, a significant difference existed between the groups for uNOx (p = 0.001; nonoptimal: 933.5 8 140.4, optimal: 425.0 8 52.6 mol/gCr), and for hsCRP (p = 0.018, nonoptimal: 3.9 8 0.7, optimal: 1.9 8 0.6 mg/l). Significant inReceived: January 5, 2010 Accepted: May 21, 2010 Published online: July 13, 2010 Deborah L. Feairheller Department of Kinesiology, Temple University 1800 N. Broad Street Philadelphia, PA 19122 (USA) Tel. +1 215 204 6216, Fax +1 215 204 4414, E-Mail dfeairheller @ gmail.com © 2010 S. Karger AG, Basel Accessible online at: www.karger.com/kbr Nitric Oxide, Renal Function and PHTN in African-American Women Kidney Blood Press Res 2010;33:282–290 283 HTN [4–6] . Recently, plasma levels of high-sensitivity Creactive protein (hsCRP), an acute-phase hepatic protein, have been related to impaired renal function and HTN [7, 8] . On the other hand, results from independent studies on the endogenous vasodilator nitric oxide (NO) conflict because some studies suggest a deficiency in NO with ESRD and HTN [9] , while others report upregulated NO production [10] . NO serves as a potent vasodilator that is produced through oxidation of L -arginine to L -citrulline and released from the endothelial layer of blood vessels [11] . Vascular NO levels serve to maintain endothelial function either mechanically through augmented smooth muscle relaxation, or chemically through the rapid inactivation of the superoxide radical (O2 – ) [12] . In fact, within the renal system, NO exerts a powerful influence on the regulation of glomerular filtration rate (GFR) and sodium (Na + ) excretion [13] . Pre-hypertension (PHTN) is known to be a predictor for the future development of HTN. PHTN is a blood pressure (BP) classification defined by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) as systolic BP between 120 and 139 mm Hg and diastolic BP between 80 and 89 mm Hg [14] . Individuals with PHTN are likely to develop HTN within 5 years, yet the factors involved in this transition remain unclear. The impact of PHTN in African-American women on the development of ESRD and subsequent CVD progression may be substantial, since African-Americans are more likely to develop PHTN at younger ages and its presence is associated with future atherosclerosis [15] . Data from the Women’s Health Initiative Study suggests that women with PHTN are at increased risk for CVD events [16] . Recently, a few population-based studies have reported that the risk of renal disease may extend to PHTN, but defining the BP levels at which this risk exists needs to be determined [17–19] . Furthermore, the physiologic derangements associated with impaired renal function as seen in HTN may occur earlier during the period of PHTN and are likely to involve increased oxidative stress and inflammation as seen in frank HTN. Despite this plausibility, the relationship between BP levels in the PHTN range, renal function, inflammation, and oxidative stress remains to be fully established. It has been suggested that using 24-hour ambulatory BP (ABP) monitoring better predicts the risk of morbid events than clinical BP measurements because a 24-hour average considers the pressure load on the blood vessel system over an entire 24-hour period [20] . From this, BP values have been suggested that define the upper limits of ABP averages. ‘Optimal’ 24-hour average BP values are ! 125/75, ‘normal’ 24-hour average BP values are ! 130/80, and ‘abnormal’ 24-hour average BP values are 1 135/85 [21] . The PHTN classification range of BP by JNC 7 (systolic BP 120–139 mm Hg or diastolic BP 80–89 mm Hg) includes a larger range of BP values than those that fall primarily in the ‘normal’ 24-hour average BP range. Considering this, we used average 24-hour ABP values obtained through ABP monitoring to classify participants into BP groups in order to better compare potential effects that a PHTN BP may have on renal function and oxidative stress markers in African-American women. The purpose of our study was to compare several indices of renal function with urinary (uNOx) and plasma (pNOx) NO levels, the plasma antioxidant biomarkers superoxide dismutase (SOD) and total antioxidant capacity (TAC), and the inflammatory marker hsCRP, in AfricanAmerican women with both optimal and nonoptimal average 24-hour ABP levels. Materials and Methods This study included preand post-menopausal African-American women (n = 28) between the ages of 40–75 years (53.5 8 1) who were sedentary, nonsmokers, nondiabetics, not on lipid-lowering medications, had an average BMI of 32.1 8 1, were on no more than one antihypertensive medication, and were without any end-organ damage. Participants responded to media advertisements and underwent a telephone interview to assess their initial eligibility. The study was approved by the Institutional Review Board of Temple University, Philadelphia, Pa., USA. All participants provided their written, informed consent during their first laboratory visit. None of the women were on a hormone replacement therapy regimen. Medical histories were reviewed on the first laboratory visit to ensure they met the study inclusion criteria listed above. A 12-hour overnight fasting blood sample was drawn for blood chemistry, complete blood count, lipid profiles, serum creatinine (SCr), and hsCRP levels. Glomerular filtration rate (GFR) was calculated using the 4-variable MDRD equation specific to African-Americans: GFR (ml/min/1.73 m 2 ) = 186 ! (SCr –1.154 ) * (age –0.203 ) * (1.21) * (0.742 if female ) [22] . Participants then underwent a physical examination and a physician-supervised echocardiogram bicycle stress test to screen for any cardiovascular, pulmonary, or other chronic diseases. All qualified participants then underwent 6 weeks of dietary instruction (1 h each session) with a registered dietician instructing them on how to maintain the American Heart Association low-fat ( ! 30% total calorie intake) and low-sodium ( ! 3 g/day) diet. Participants had to follow this prescribed diet continuously throughout the dietary instruction period and be weight stable before undergoing any testing. Under close supervision of the study physician, any woman using one antihypertensive medication was tapered off the medication and remained off of their medication for the duration of the study. At the completion of the 6 weeks, a submaximal treadmill (TM) exercise test was performed to measure the volume of oxygen con-