Cyclooxygenase-2 Selectively Controls Renal Blood Flow Through a Novel PPAR{beta}/{delta}-Dependent Vasodilator PathwayNovelty and Significance [Cyclooxgenase and Renal Blood Flow]
Cyclooxygenase-2 (COX-2) is an inducible enzyme expressed in inflammation and cancer targeted by nonsteroidal anti-inflammatory drugs. COX-2 is also expressed constitutively in discreet locations where its inhibition drives gastrointestinal and cardiovascular/renal side effects. Constitutive COX-2 expression in the kidney regulates renal function and blood flow; however, the global relevance of the kidney versus other tissues to COX-2–dependent blood flow regulation is not known. Here, we used a microsphere deposition technique and pharmacological COX-2 inhibition to map the contribution of COX-2 to regional blood flow in mice and compared this to COX-2 expression patterns using luciferase reporter mice. Across all tissues studied, COX-2 inhibition altered blood flow predominantly in the kidney, with some effects also seen in the spleen, adipose, and testes. Of these sites, only the kidney displayed appreciable local COX-2 expression. As the main site where COX-2 regulates blood flow, we next analyzed the pathways involved in kidney vascular responses using a novel technique of video imaging small arteries in living tissue slices. We found that the protective effect of COX-2 on renal vascular function was associated with prostacyclin signaling through PPARβ/δ (peroxisome proliferator-activated receptor-β/δ). These data demonstrate the kidney as the principle site in the body where local COX-2 controls blood flow and identifies a previously unreported PPARβ/δ-mediated ...
Source: Hypertension - Category: Cardiology Authors: Nicholas S. Kirkby, Walkyria Sampaio, Gisele Etelvino, Daniele T. Alves, Katie L. Anders, Rafael Temponi, Fisnik Shala, Anitha S. Nair, Blerina Ahmetaj-Shala, Jing Jiao, Harvey R. Herschman, Wang Xiaomeng, Walter Wahli, Robson A. Santos, Jane A. Mitchell Tags: Basic Science Research, Endothelium/Vascular Type/Nitric Oxide, Vascular Disease Original Articles Source Type: research
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