Lead increases aldosterone production by rat adrenal cells.
Exposure to lead has been postulated to contribute to elevated blood pressure in humans and has been shown to raise blood pressure in animals. The mechanism of action of lead on blood pressure is unknown. We fed lead to rats in their drinking water and then examined the production of aldosterone by their adrenal cells in vitro. We also measured excretion of aldosterone and corticosterone by intact rats stimulated with corticotropin, with and without lead treatment. At a dose (273 ppm) that raised blood levels to 30 to 40 micrograms/dL, comparable to blood levels in exposed humans, lead induced increased aldosterone secretion in vitro and in vivo. The effect of lead was most evident when cells or animals were stimulated with aldosterone secretagogues. Experiments in vitro indicate that exposure to lead in vivo increases activity of one or more steps in the late pathway of aldosterone biosynthesis. The results suggest that the hypertensive effect of lead involves relative hyperaldosteronism and may be most evident when secretion of this hormone is stimulated.
Goodfriend
T L
TL
William S. Middleton Memorial Veterans Hospital, Madison, WI 53705, USA.
Ball
D L
DL
Elliott
M E
ME
Shackleton
C
C
D000311:Adrenal Glands / Q000166:cytology / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000096:biosynthesis* / Q000652:urine; D000804:Angiotensin II / Q000494:pharmacology; D000809:Angiotensins / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003345:Corticosterone / Q000652:urine; D004305:Dose-Response Relationship, Drug; D007854:Lead / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D015430:Weight Gain / Q000187:drug effects
D000809:Angiotensins; D000804:Angiotensin II; D007854:Lead; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone