Amiloride, a specific drug for hypertension in black people with T594M variant?
The T594M polymorphism of the epithelial sodium channel is found in approximately 5% of people of African origin and is significantly associated with high blood pressure. Although the T594M polymorphism could increase renal sodium absorption through affected channels, it is not known whether this polymorphism causes hypertension. Amiloride specifically inhibits overactive sodium channels and effectively controls blood pressure in Liddle's syndrome, in which hypertension is caused by separate epithelial sodium channel mutations. The aim of this study was to determine whether amiloride was effective in lowering blood pressure in individuals with the T594M polymorphism. In an open, controlled study, 14 black hypertensive individuals with the T594M polymorphism were withdrawn from their usual medication and treated with amiloride. On entry to the study, individuals taking a mean of 2 drugs had blood pressure of 142/89+/-3/3 mm Hg. Amiloride alone (10 mg BID) controlled blood pressure effectively to the same level (140/91+/-4/2 mm Hg). When amiloride was withdrawn for 2 weeks, there was a large increase in blood pressure of 17/8+/-4/2 mm Hg (systolic, P<0.05; diastolic, P<0.01). On restarting amiloride, blood pressure was again controlled to 140/88+/-6/2 mm Hg. These results demonstrate that 10 mg BID amiloride is effective in controlling blood pressure in hypertensive individuals of African origin who have the T594M polymorphism. Our study supports the concept that the T594M polymorphism contributes to the elevation of blood pressure and suggests that consideration should be given to the use of amiloride in affected individuals.
Baker
Emma H
EH
Department of Physiological Medicine, St George's Hospital Medical School, Cranmer Terrace, London, United Kingdom. ebaker@sghms.ac.uk
Duggal
Ajay
A
Dong
Yanbin
Y
Ireson
Nicola J
NJ
Wood
Monique
M
Markandu
Nirmala D
ND
MacGregor
Graham A
GA
D000450:Aldosterone / Q000097:blood; D000584:Amiloride / Q000627:therapeutic use*; D019943:Amino Acid Substitution; D009320:Atrial Natriuretic Factor / Q000097:blood; D044383:Black People / Q000235:genetics*; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D004232:Diuretics / Q000627:therapeutic use*; D053503:Epithelial Sodium Channels; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D008137:Longitudinal Studies; D011110:Polymorphism, Genetic; D012083:Renin / Q000097:blood; D015222:Sodium Channels / Q000235:genetics*; D016896:Treatment Outcome
D004232:Diuretics; D053503:Epithelial Sodium Channels; D015222:Sodium Channels; D000450:Aldosterone; D000584:Amiloride; D009320:Atrial Natriuretic Factor; D012083:Renin