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Contributions of the sympathetic nervous system, glutathione, body mass and gender to blood pressure increase with normal aging: influence of heredity.

Kennedy BP, Rao F, Botiglieri T, Sharma S, Lillie EO, Ziegler MG, O'connor DT

Department of Medicine and Center for Molecular Genetics, University of California at San Diego, CA 92093-0838, USA.

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 (NEu), and plasma GSH in n=204 twins across the age spectrum. BP correlated directly with BMI, NEpl, and NEu, but inversely with GSH. Age correlated with BP, BMI, NEpl, and NEu. BP, BMI, NEpl, and NEu were higher in older subjects than younger subjects, whereas GSH was lower with aging. In older subjects with high (above median) NEpl, 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. NEu was significantly reduced in young high-BMI subjects vs young low-BMI subjects. The heritability (h2) of NEpl, NEu, and GSH ranged from approximately 50 to approximately 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 h(2) for plasma GSH, NE, and urine NE suggests that such traits may be useful 'intermediate phenotypes' in the search for genetic determinants of BP.

Published 22 November 2005 in J Hum Hypertens, 19(12): 951-69.
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