Selective ENaC blocker, amiloride, is effective in reducing blood pressure in blacks with T594M polymorphism of ENaC. Every population is heterogenous for salt-sensitivity. It is thus of interest whether amiloride will block the channel in salt-resistant individuals as well as salt-sensitive persons with or without β-ENaC polymorphism especially as amiloride has been suggested as a sole anti-hypertensive agent in blacks [1]. 22 normotensive (NT) and 42 age-matched hypertensive (HT) subjects earlier divided into salt-sensitive (SS) (NT = 11; HT = 22) and salt-resistant (SR) (NT = 11; HT = 20) subgroups [2] took part in the study. Blood pressure (BP) was measured before and after they were salt-loaded with 200mmol Na+/day for 5 days. After one week wash-out period, subjects ingested a combination of the salt-load and 5mg amiloride tablets daily for 5 days. The effect of the combination on blood pressure was then determined. Blood was also sequenced for β-ENaC polymorphisms [3]. Ethical clearance for this study was obtained from the College of Medicine, University of Lagos. Data are presented as mean ± S.E.M., compared with ANOVA and appropriate post-hoc tests. Baseline systolic (SBP) and diastolic blood pressures (DBP) were similar (p>0.05) in the SS (SBP 121.5±2.8 mmHg; DBP 80.9±0.8 mmHg) and SR (SBP 120.7±2.4 mmHg; DBP 80.2±1.6 mmHg) NT subjects and among the SS (SBP 144.7±3.6 mmHg; DBP 92.9±2.4 mmHg) and SR (142.9±4.8 mmHg; DBP 99.2±2.0 mmHg) HT subjects. Following the salt-load, BP changed significantly (p<0.01) (+7.7±2.6% SBP; +11.6±2.1% DBP) among the SS NT subjects but marginally (p>0.05) (+0.6±1.9% SBP; -0.5±2.6% DBP) among the SR NT subjects. Similarly, there were significant (p <0.001) pressor responses to the salt load among the SS (+7.8±1.7% SBP; +11.6±1.7% DBP) but not among the SR (SBP +2.1±1.7%; DBP -2.2±1.4%) HT subjects. Amiloride plus salt-loading led to significant reduction in SBP among SS (p<0.001) (-9.9±2.1% NT; -12.9±2.0% HT) and SR subjects (p<0.05) (-6.5±2.0% NT; -10.0±1.5% HT) when compared with salt-loading alone. Similarly, the combination significantly reduced DBP among SS (p<0.001) (-13.9±3.4% NT; -10.4±2.8% HT) subjects but reduced DBP in SR (-7.1±1.7%, p<0.001) HT subjects only. 7 out of 11 subjects with ENaC polymorphism were HT (4 SS and 3SR). However there was no relationship between ENaC status and salt sensitivity, with respect to SBP, as the effect of ENaC blockade by amiloride are similar in both SS (-12.6±7.7%) and SR (-16.5±6.2%) HT subjects P=0.59). However in SR HT subjects, fall in DBP was significantly (P<0.01) less in SR (-7.0±3.5%) than in SS (-21.4±1.6%). These preliminary results suggest that in SR HT, β-ENaC polymorphism may be associated with reduced DBP responsiveness to amiloride.
Physiology 2014 (London, UK) (2014) Proc Physiol Soc 31, PCA101
Poster Communications: Effect of amiloride on salt-sensitive and salt-resistant adult Nigerian subjects with and without ╬▓-ENaC polymorphisms
S. O. Elias1, O. A. Sofola2, S. I. Jaja2
1. Physiology, Lagos State University College of Medicine, Lagos, Nigeria. 2. Physiology, College of Medicine of The University of Lagos, Lagos, Nigeria.
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Where applicable, experiments conform with Society ethical requirements.