Premium
Anandamide and its metabolites as novel natriuretic and antihypertensive lipids from the renal medulla
Author(s) -
Ritter Joseph K,
Li Cao,
Xia Min,
Li Caixia,
Lichtman Aron,
Li Pin-Lan
Publication year - 2012
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.26.1_supplement.1105.10
Subject(s) - endocrinology , medicine , anandamide , kidney , chemistry , renal medulla , arachidonic acid , renal function , renal blood flow , endocannabinoid system , biology , enzyme , cannabinoid receptor , biochemistry , antagonist , receptor
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 well understood. This study characterized the distribution of AEA and its metabolizing enzymes and assessed their functions in the kidney. AEA measured by LC‐MS/MS was higher in the renal medulla (Med) versus cortex (Cort) of C57BL6 mice. AEA infused into the medulla (15–60 nmol/kg/min) dosedependently increased the urine formation rate and sodium excretion. The effects were blocked by systemic infusion (0.1 μg/kg/min) of celecoxib, an inhibitor of cyclooxygenase 2 (COX‐2), which converts AEA to prostamide E2 (PE2). Western and IHC analyses of COX‐2 and the AEA‐hydrolytic enzyme, fatty acid amide hydrolase (FAAH), showed opposite patterns of expression in the kidney with FAAH higher in Cort and COX‐2 higher in Med. This was supported by differential conversion of AEA to PE2 and arachidonic acid by mouse kidney Med and Cort microsomes, respectively. In anesthetized normal mice, PE2 infused intravenously reduced mean arterial pressure, increased renal blood flow and antagonized effects of angiotensin II. These results suggest an important physiological role of AEA as an intrarenal natriuretic lipid and PE2 as a circulating lipid hormone from the renal medulla for the regulation of body fluid and arterial blood pressure. Supported by NIH grants DK54927 and DA009789