title: Cyclooxygenases, the kidney, and hypertension.
abstract: Selective cyclooxygenase (COX)-2 inhibitors that are in widespread clinical use were developed to avoid side effects of conventional NSAIDs, including gastrointestinal and renal toxicity. However, COX-2 is constitutively expressed in the kidney and is highly regulated in response to alterations in intravascular volume. COX-2 metabolites have been implicated in maintenance of renal blood flow, mediation of renin release, and regulation of sodium excretion. COX-2 inhibition may transiently decrease urine sodium excretion in some subjects and induce mild to moderate elevation of blood pressure. Furthermore, in conditions of relative intravascular volume depletion and/or renal hypoperfusion, interference with COX-2 activity can have deleterious effects on maintenance of renal blood flow and glomerular filtration rate. In addition to physiological regulation of COX-2 expression in the kidney, increased renal cortical COX-2 expression is seen in experimental models associated with altered renal hemodynamics and progressive renal injury (decreased renal mass, poorly controlled diabetes), and long-term treatment with selective COX-2 inhibitors ameliorates functional and structural renal damage in these conditions.
authors.affiliation: Division of Nephrology, S 3322 MCN, Vanderbilt University School of Medicine, Nashville, TN 37232-2372, USA.
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Cheng
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Harris
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D006801:Humans; D006973:Hypertension / Q000209:etiology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007668:Kidney / Q000201:enzymology*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases