Stress-Induced Sodium Excretion

Abstract

Abstract-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 (⌬U Na Vϭstress U Na VϪ 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: 17.6Ϯ3.3 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 ⌬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 ⌬U Na V were 0.36 in whites and 0.39 in blacks. In summary, this study establishes ⌬U Na V and stress U Na V as heritable phenotypes that may be used to study the genetic etiology of early hypertension development. Key Words: natriuresis Ⅲ blood pressure Ⅲ risk factors Ⅲ genetics Ⅲ twin study Ⅲ black T he key role of the kidney in long-term blood pressure (BP) regulation is generally recognized 1,2 and includes sodium handling in response to extended periods of stress. 3 We showed recently that individuals without an adequate compensatory increase in the urinary sodium excretion (U Na V) rate in response to a stress-induced BP increase (ie, impaired stress-induced pressure natriuresis [SIPN]) show a delayed BP recovery after stress, which seemed to be at least partly because of their increased blood volume. 4 For the same level of stress, individuals who show impaired SIPN are, therefore, exposed to a greater cardiovascular and renal load, which may lead to the premature development of essential hypertension and its sequelae. 4,5 This scenario was supported by a recent study in which we observed that adolescent black subjects with impaired SIPN showed a higher albumin excretion rate than those with normal sodium excretion. 6 We previously proposed a gene-environment interaction model of stress-induced hypertension in which we integrated both short-term (cardiovascular) and long-term (renal) BP regulatory pathways. 3,7,8 Several studies suggest the importance of genetic influence on the renal handling of sodium, but evidence is indirect with regard to the renal response to stress. 3 For example, the heritability ...

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