1. ¹Department of Medicine and Center for Molecular Genetics, University of California at San Diego, and VA San Diego Healthcare System, San Diego, CA, USA
2. ²Baylor Institute for Metabolic Diseases, Dallas, TX, USA

Correspondence: Dr DT O'Connor or Dr MG Ziegler, Department of Medicine (0838), UCSD School of Medicine and VASDHS, 9500 Gilman Drive, La Jolla, CA 92093-0838, USA. E-mail: doconnor@ucsd.edu or mziegler@ucsd.edu; URL: http://www.medicine.ucsd.edu/hypertension

³These two authors contributed equally to this work.

Deceased.

Received 30 September 2004; Revised 8 June 2005; Accepted 15 June 2005; Published online 29 September 2005.

Abstract

Body mass and sympathetic activity increase with aging and might underlie blood pressure (BP) elevation. Increased body mass index (BMI) may elevate BP by increasing sympathetic activity. Glutathione (GSH) can decrease BP, and declines with aging. We measured systolic (SBP) and diastolic BP, BMI, plasma (NE_pl) and urine norepinephrine (NE_u), and plasma GSH in n=204 twins across the age spectrum. BP correlated directly with BMI, NE_pl, and NE_u, but inversely with GSH. Age correlated with BP, BMI, NE_pl, and NE_u. BP, BMI, NE_pl, and NE_u were higher in older subjects than younger subjects, whereas GSH was lower with aging. In older subjects with high (above median) NE_pl, SBP was 8 mmHg higher than in those of comparable age with low NE. In younger subjects with high GSH, BP was significantly lower than in younger subjects having low GSH. NE_u was significantly reduced in young high-BMI subjects vs young low-BMI subjects. The heritability (h²) of NE_pl, NE_u, and GSH ranged from 50 to 70%, and these biochemical quantities were considerably more heritable than BP. We conclude that increases in sympathetic activity contribute to aging-induced SBP elevations, especially in older females. GSH reductions apparently participate in aging-induced BP elevations, most strongly in males. BMI increases contribute to BP elevations, particularly in younger subjects. BMI elevations apparently raise BP mainly by peripheral mechanisms, with generally little sympathetic activation. Substantial h² for plasma GSH, NE, and urine NE suggests that such traits may be useful 'intermediate phenotypes' in the search for genetic determinants of BP.