Alterations in aldosterone biosynthesis in essential hypertensives.
We studied hypertensives with decreased adrenal responsiveness to infused angiotensin II (AII) to assess their responsiveness to other aldosterone secretagogues, ACTH and potassium, which are thought to stimulate aldosterone synthesis in sites different from one another and from AII. All subjects, following sodium restriction, received an infusion of AII in increasing doses (0.1-3 ng/kg per min). The increment in aldosterone between control and the highest infusion dose divided by the increment in plasma AII was used as the index of adrenal responsiveness. All normotensive controls (NC) had a ratio greater than 0.5. Hypertensives with a normal ratio were designated normal responders (NR) and those with a lower ratio were abnormal responders (AbR). The slope of the regression line between aldosterone and AII was significantly less for the AbR (0.02 +/- 0.04) than for the NR (1.20 +/- 0.02, P less than 0.001) and the NC (1.00 +/- 0.03, P less than 0.001) groups. During infusion of cosyntropin in increasing doses (0.05-1.5 mIU/kg per 30 min), the aldosterone response of the AbR was significantly less than that of the NR (P less than 0.016) or the NC (P less than 0.05) groups. Similarly, after infusion of potassium (0.33 mEq/min), the increment in aldosterone in the AbR group (7.6 +/- 2.2 ng/dl) was significantly less than that in the NR (14.2 +/- 2.5 ng/dl, P less than 0.05) and the NC (18 +/- 5 ng/dl, P less than 0.05) groups. Thus hypertensives with decreased aldosterone responsiveness to infused AII also had decreased responsiveness to infused ACTH and potassium, suggesting that their defect lies in the intracellular aldosterone biosynthetic pathway.
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000450:Aldosterone / Q000096:biosynthesis* / Q000097:blood; D000804:Angiotensin II / Q000494:pharmacology*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D008875:Middle Aged; D011188:Potassium / Q000097:blood; D012083:Renin / Q000097:blood
D000804:Angiotensin II; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D012083:Renin; D011188:Potassium