title: Dexamethasone-induced diuresis is associated with inhibition of the renin-angiotensin-aldosterone system in rats.
abstract: In heart failure (HF) patients, diuretics remain the cornerstone of therapy to relieve fluid retention. However, the resulting volume loss activates the renin-angiotensin-aldosterone system (RAAS), which blunts the decline in volume depletion and blood pressure. RAAS activation, in turn, compromises the diuretic decongesting effect. Although corticosteroids can induce potent diuresis in HF patients, the effects of corticosteroids on RAAS activation remain unclear. Therefore, we assessed the effects of dexamethasone (Dex) on urine output and plasma angiotensin II and aldosterone levels in rats following water deprivation-induced dehydration, following induction of chronic HF (CHF), and following induction of CHF and volume expansion therapy. In the dehydration model, Dex significantly increased urine output and inhibited dehydration-induced RAAS activation. This favorable effect was abolished by the glucocorticoid receptor antagonist RU486, suggesting involvement of the glucocorticoid receptor. In the CHF model, Dex treatments doubled urine output without activating RAAS. Moreover, in acute volume expansion experiments, Dex pretreatments led to potent diuresis during the pretreatment period and restored renal adaptation to acute volume expansion without activating RAAS in rats with CHF. Collectively, these data show that corticosteroids induce potent diuresis without activating RAAS in rats.
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, China; Cardiology Division, The First Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Ge
authors.affiliation: Cardiology Division, The First Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Jian-Long
authors.initials: JL
authors.lastname: Zhai
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, China; Department of Pharmacology, Hebei Academy of Medical Sciences, Shijiazhuang, China. Electronic address: zhangjx100@163.com.
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002908:Chronic Disease; D003681:Dehydration / Q000473:pathology; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004231:Diuresis / Q000187:drug effects*; D006333:Heart Failure / Q000188:drug therapy; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013997:Time Factors
chemical_list: D015735:Mifepristone; D003907:Dexamethasone
keywords: Aldosterone; Angiotensin II; Dexamethasone; Diuresis; Heart failure