The effect of salt intake and the T594M [beta]-sodium channel polymorphism on blood pressure in black people of African origin

High blood pressure is more common in black individuals of African origin than in other ethnic groups. It is thought that inherited differences in renal salt handling may, in part, account for the increased risk of high blood pressure in black individuals. The work in thesis aims to investigate the effects of both salt reduction and of a genetic polymorphism in one of the renal sodium handling mechanisms, the epithelial sodium channel (ENaC), on blood pressure and renal target organ damage in black individuals. The first clinical study in this thesis has examined the effects of modest salt reduction, from approximately 12 to 6 grams daily, on blood pressure and urine protein excretion in black hypertensives. Results show that salt reduction significantly reduces blood pressure and urine protein excretion. A further, much smaller, pilot study in black nohnotensiv~s demonstrated a small but significant fall in the mean 24hour systolic blood pressure following similar modest salt reduction. Further studies were conducted in order to explore the role of the T594M ENaC polymorphism on blood pressure in black individuals. We looked for evidence of ENaC over activity in the group that carried the T594M polymorphism. A case controlled study in black individuals with and without the polymorphism did not demonstrate any phenotypic differences between cases and controls. Data from the previous salt reduction study in black hypertensives was then re-analysed to determine if the T594M genetic status influenced the blood pressure response to salt. Numbers with the polymorphism in this study, however, were too small to demonstrate a significant difference between the two groups. A larger randomised controlled trial of amiloride and spironolactone in black hypertensives with and 4 • ) without the T594M polymorphism was also carried out and found no specific pharmacogenetic relationship between the T594M polymorphism and blood pressure response to amiloride.EThOS - Electronic Theses Online ServiceGBUnited Kingdo