Stress-induced sodium excretion: a new intermediate phenotype to study the early genetic etiology of hypertension?

Impaired stress-induced pressure natriuresis, ie, an inadequate compensatory increase in urinary sodium excretion (U(Na)V) in response to a stress-induced blood pressure increase, may lead to the premature development of essential hypertension. To assess the heritability of baseline U(Na)V, stress U(Na)V, and the U(Na)V response to stress (Delta U(Na)V=stress U(Na)V- baseline U(Na)V), we studied 396 black and 494 white twins, including monozygotic and dizygotic twins of the same as well as the opposite sex (mean age: 17.6+/-3.3 years; range: 11.9 to 30.0 years). Bivariate genetic model fitting was performed to examine the extent to which genetic and environmental factors are common or specific to baseline and stress U(Na)V. Heritability estimates for Delta U(Na)V can be derived from these bivariate models. All of the bivariate analyses were performed separately in whites and blacks, because univariate models for baseline U(Na)V showed significant ethnic differences in heritability estimates. Best-fitting models showed that the heritability of stress U(Na)V was 0.42 in whites and 0.58 in blacks. Only 15% and 11% of the total variance could be attributed to genetic factors common to baseline and stress U(Na)V in whites and blacks, respectively. After removal of all of the shared influences with baseline U(Na)V, heritabilities for stress U(Na)V were 0.32 in whites and 0.57 in blacks. Heritability estimates for Delta U(Na)V were 0.36 in whites and 0.39 in blacks. In summary, this study establishes Delta U(Na)V and stress U(Na)V as heritable phenotypes that may be used to study the genetic etiology of early hypertension development.