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We sought to determine the effect of amiloride on blood pressure (BP) and the presence of polymorphisms of the β-subunit of the epithelial sodium channel (ENaC) among normotensive (NT) and hypertensive (HT) Nigerians. Healthy volunteers—47 NT and 53 age-matched HT were recruited after giving informed consent. Subjects were salt-loaded with 200 mmol of NaCl daily for 5 days. Following a week washout period, salt-loading was repeated in addition to the administration of 5 mg amiloride daily for five days. Blood pressure, plasma and urine electrolytes were measured at baseline, after salt-loading and after salt-loading plus amiloride. PCR amplicons were sequenced for β-ENaC polymorphisms. Salt-loading led to a significant increase (p < 0.05) in SBP among NT and HT and in DBP (p < 0.001) only among HT. Amiloride reduced SBP and DBP to below baseline levels in NT (p < 0.05) and HT (p < 0.001) subjects. Five of the subjects had the β-T594M polymorphism, HT 3/53; NT 2/47 (p = 0.75). Four previously unreported β-ENaC mutations were recorded: E632V and E636V, respectively, among two HT subjects, D638Y in another HT and L628Q in one NT subject. We showed the presence of β-ENaC polymorphisms among our populace and the possible usefulness of amiloride as a single antihypertensive among Nigerians. [ABSTRACT FROM AUTHOR]