Genetics, salt, and stress are three of the factors contributing to the higher prevalence of essential hypertension (EH) in blacks as compared to whites.We demonstrated a significant percentage of black youth with a reduced compensatory increase in urinary sodium excretion (UNaV) in response to stress-induced increase in blood pressure (BP).We refer to this pattern of response as “impaired stress-induced pressure natriuresis (SIPN)”.The epithelial sodium channel (ENaC) constitutes the rate-limiting step for renal sodium reabsorption.Two polymorphisms of the ENaC gene, T594M and G442V, were almost exclusively expressed in blacks. This study was to test the hypothesis that carriers of the 594M or 442V allele show impaired SIPN.The subjects were 108 black normotensives aged 16–19 years.Upon arrival the subjects voided, and a pre-stress urine sample was obtained.The subjects then performed two reactivity tasks, a video game challenge and forehead cold stimulation followed by a post-stress urine sample.BP was obtained throughout the tasks and averaged to obtain a measure of BP that was concurrent with the measure of UNaV. The T594M and G442V polymorphisms were genotyped by enzyme digestion assays.Gene by environment interaction hypothesis was statistically evaluated by analyzing the difference in the pre- and post-stress tests (UNaV and BP) between carriers and non-carriers.Of the 108 subjects, there were 11 carriers of the 594M allele.Carriers had approximately 50% less ΔUNaV (stress UNaV – pre-stress UNaV, mean ± standard error) compared to non-carriers, 2.40±1.69 versus 4.59±0.57 mEq/hr, p=0.10 (one tailed, exact permutation test).The difference in ΔBP (stress BP- pre-stress BP) between carriers and non-carriers was small (16.68±3.02 versus 19.27±1.02mmHg, p=0.42). There were 25 carriers of the 442V allele.Carriers of the 442V allele and non-carriers had similar levels of ΔBP (20.44±2.00 versus 18.58±1.10, p=0.42) and ΔUNaV (4.36±1.13 versus 4.37±0.62, p=0.1).These results suggest that carriers of the 594M allele may be characterized by impaired SIPN.Our findings are preliminary and will need to be verified using larger samples possessing greater statistical power.Genetic factors may play a role in the natriuretic response to environmental stress, supporting a gene by environment interaction model for the development of EH in blacks. Am J Hypertens (2004) 17, 196A–196A; doi: 10.1016/j.amjhyper.2004.03.517