Programming of hypertension: associations of plasma aldosterone in adult men and women with birthweight, cortisol, and blood pressure.
Animal models suggest that explanations for the association of low birthweight with adult hypertension may include chronic activation of the hypothalamic-pituitary-adrenal or renin-angiotensin-aldosterone axes. In humans, low birthweight predicts elevated plasma cortisol, but associations with aldosterone have not been reported. We measured aldosterone in serum samples from 205 men and 106 women from 67 to 78 years of age, from Hertfordshire, UK, for whom birthweight was recorded. Participants underwent an overnight low-dose (0.25 mg) dexamethasone suppression test and a low-dose (1 mug) ACTH (corticotropin) stimulation test and were genotyped for the -344 C/T polymorphism of the CYP11B2 gene encoding aldosterone synthase. Median aldosterone was 6.22 ng/dL (range 0.15 to 38.74) and was higher in men than women (P<0.0001). Higher aldosterone levels after both dexamethasone and ACTH stimulation were associated with higher blood pressure (r=0.20, P=0.001; r=0.33, P<0.0001, respectively) and with lower birthweight (r=-0.16, P=0.008; r=-0.21, P=0.001, respectively). These associations remained significant after adjusting for age, gender, obesity, and genotype. Our findings supplement previous evidence that aldosterone is an important regulator of blood pressure and suggest that factors in early life that retard fetal growth and program activation of the hypothalamic-pituitary-adrenal axis in humans result not only in higher glucocorticoid activity but also in increased mineralocorticoid activity.
Reynolds
Rebecca M
RM
Endocrinology Unit, Centre for Cardiovascular Sciences, Queen's Medical Research Institute, Edinburgh, UK. R.Reynolds@ed.ac.uk
Walker
Brian R
BR
Phillips
David I
DI
Dennison
Elaine M
EM
Fraser
Robert
R
Mackenzie
Scott M
SM
Davies
Eleanor
E
Connell
John M
JM
D000324:Adrenocorticotropic Hormone; D000367:Age Factors; D000368:Aged; D000450:Aldosterone / Q000097:blood* / Q000378:metabolism; D000704:Analysis of Variance; D001724:Birth Weight; D001795:Blood Pressure Determination; D015331:Cohort Studies; D003907:Dexamethasone; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D006973:Hypertension / Q000097:blood* / Q000175:diagnosis* / Q000503:physiopathology; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D010913:Pituitary-Adrenal System / Q000502:physiology; D011336:Probability; D012307:Risk Factors; D012737:Sex Factors; D018709:Statistics, Nonparametric
D000450:Aldosterone; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone