Function of dynamically stimulated endothelium and renin–angiotensin–aldosterone system in normotensive subjects with a family history of hypertension

Abstract

Genetic influences on the acute stimulation of the renin-angiotensin-aldosterone system (RAAS) and on endothelial activation were studied by examining healthy blood donors with and without hypertensive parents. Healthy blood donors were assigned to two groups, according to the presence or absence of a parental history of hypertension. Plasma levels of renin, nitric oxide (NO) and plasminogen activator inhibitor 1 (PAI-1) were studied before and after acute alterations in renal perfusion induced by phlebotomy, and the two groups compared. During phlebotomy, 400-500 mL of blood was extracted from each subject, with that volume varying relative to each subject's body surface area (m(2)). No statistically significant inter-group differences were observed between the baseline mean levels of plasma renin, NO or PAI-1. After phlebotomy, significant increases were detected in mean plasma renin activity (PRA) and NO levels and in PAI-1 activity (P < 0.001). However, the increases in mean PRA (P < 0.05) level and PAI-1 activity (P < 0.05) were more pronounced in those with hypertensive parents than those without; conversely, the increase in NO levels was more pronounced in the latter group. No statistically or clinically significant difference was found between the mean body mass indices of these two groups. Only two subjects were overweight, and none were obese; the remainder had weights that were normal. We found no significant correlation between body mass index and either NO or PAI-1 level. Post-phlebotomy, PRA and PAI-1 responses were more dramatic, but the NO response less in normotensive subjects having a parental history of hypertension, suggesting that these changes may represent familial, possibly genetic influences before overt hypertension occurs.