Prostaglandins: Kinins and Angiotensin Interactions

New York Medical College, Valhalla NY

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Abstract

DESCRIPTION (provided by applicant): The epoxide products of the cytochrome P450 system, epoxyeicosatrienoic acids (EETs), are anti-inflammatory, thrombolytic and antiproliferative in addition to being vasoactive and natriuretic. Activating the renal Adenosine-A2A-receptor stimulates EET synthesis, a major factor in the renal response to injury. The sphere of activity of the renal Adenosine-A2A-receptor-EET system has been enlarged by linking its activity to salt intake. The proposed studies examine critical determinants of the activity of the Adenosine-A2A-receptor-EET system: 1) Tumor necrosis factor and generation of reactive oxygen species (ROS). 2) ROS, 5'-Nucleotidase (5'-NT) activity and Adenosine production resulting in increased EET synthesis in response to activation of the A2A receptor. 3) Heme oxygenase activity and suppression of EET and 20-HETE synthesis. 4) Activation of peroxisome-proliferator-activated receptor alpha by Fibrates with stimulation of EET synthesis.