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The Anandamide Cyclooxygenase‐2 Metabolite, Prostamide E2, as a Novel Diuretic and Natriuretic Lipid in the Mouse Renal Medulla
Author(s) -
Ritter Joseph K,
Li Cao,
Xia Min,
Boini Krishna M.,
Lichtman Aron H.,
Li PinLan
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.703.7
Subject(s) - natriuresis , endocrinology , medicine , chemistry , kidney , hydrochlorothiazide , diuresis , renal medulla , blood pressure
Anandamide (AEA) is an arachidonate derivative found at high levels in the kidney, but its physiological roles in the regulation of renal function are not yet well understood. In anesthetized mice, AEA infused into the renal medulla (15–60 nmol/kg/min) increased urine volume and sodium excretion. These effects were blocked by intravenous celecoxib (0.1 μg/kg/min), suggesting a role for a COX‐2 metabolite of AEA. In agreement with this hypothesis, intramedullary infusion of prostamide E2 (PE2), the major prostamide formed by mouse kidney homogenates incubated with AEA, increased urine formation and sodium excretion in a dose‐dependent manner. Furthermore, both AEA and PE2 were found to enhance the pressure natriuresis. Compared with control mice, AEA or PE2 doubled the natriuretic response when renal perfusion pressure was elevated from 95 to 125 mmHg, and AEA‐induced enhancement of pressure‐natriuresis was blocked by celecoxib. More mechanistic studies revealed that the PE2‐induced diuresis and natriuresis were substantially blunted when these mice were pretreated with hydrochlorothiazide, but not with furosemide or amiloride. These results suggest that PE2 is a novel natriuretic lipid that may act on the distal tubules to inhibit sodium reabsorption and that its enhancing action on pressure‐natriuresis may represent an important renal medullary antihypertensive mechanism. Supported by NIH grants DK54927 and DA009789.