Acetaminophen Increases Aldosterone Secretion While Suppressing Cortisol and Androgens: A Possible Link to Increased Risk of Hypertension
2016 (English)In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 29, no 10, 1158-1164 p.Article in journal (Refereed) Published
Acetaminophen (paracetamol) is a widely used analgesic and antipyretic drug. Potential side effects are of public health concern, and liver toxicity from acute overdose is well known. More recently, a regular use of acetaminophen has been associated with an increased risk of hypertension. We investigated effects of acetaminophen on steroidogenesis as a possible mechanism for the hypertensive action by using the human adrenocortical cell line, H295R. Cells were treated with 0.1, 0.5, and 1mM of acetaminophen for 24 hours, and secretion of steroids and gene expression of key steps in the steroidogenesis were investigated. Progesterone and aldosterone secretion were increased dose dependently, while secretion of 17 alpha-OH-progesterone and cortisol as well as dehydroepiandrosterone and androstenedione was decreased. CYP17 alpha-hydroxylase activity, assessed by the ratio 17 alpha-OH-progesterone/progesterone, and CYP17-lyase activity, assessed by the ratio androstenedione/17 alpha-OH-progesterone, were both dose-dependently decreased by acetaminophen. No effects were revealed on cell viability. Treatment of cells with 0.5mM of acetaminophen did not cause any effects on the expression of 10 genes in the steroidogenic pathways. The pattern of steroid secretion caused by acetaminophen can be explained by inhibition of CYP17A1 enzyme activity. A decreased secretion of glucocorticoids and androgens, as demonstrated by acetaminophen, would, in an in vivo situation, induce adrenocorticotropic hormone release via negative feedback in the hypothalamic-pituitary-adrenal axis and result in an upregulation of aldosterone secretion. Our results suggest a novel possible mechanism for acetaminophen-induced hypertension, which needs to be further elucidated in clinical investigations.
Place, publisher, year, edition, pages
2016. Vol. 29, no 10, 1158-1164 p.
blood pressure, acetaminophen, paracetamol, hypertension, CYP17, aldosterone, steroidogenesis, H295R
Cardiac and Cardiovascular Systems
IdentifiersURN: urn:nbn:se:uu:diva-308652DOI: 10.1093/ajh/hpw055ISI: 000386017100007PubMedID: 27217499OAI: oai:DiVA.org:uu-308652DiVA: diva2:1050566
FunderSwedish Research Council Formas, 210/2004-0601