Upregulation of COX-2 protein expression in porcine macula densa with L-NAME treatment

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] COX-2 inhibitors are newly developed drugs which are widely used for controlling pain and inflammation. Blocking this enzyme impedes the production of the prostaglandins that cause pain and swelling. However certain prostaglandins are also important in maintaining blood flow to the kidneys. In addition to prostaglandins, nitric oxide is another vasodilator which is very important in modulating vascular tone and renal blood flow. Nitric oxide is produced from enzyme called nitric oxide synthase. Macula densa is a specialized structure in the kidney which co-localizes these two enzymes and is very important in maintaining the renal blood flow. The main goal of this study was to determine how diminished production of nitric oxide, which happens in some forms of hypertension and old age, affects the COX-2 expression. Adult female swine were given non specific inhibitor of nitric oxide synthase. COX-2 expression in macula densa was significantly upregulated with nitric oxide synthase inhibition. These results suggest that COX-2 products compensate for reduced production of nitric oxide. Blocking this enzyme in face of diminished nitric oxide production may have eleterious effects on renal flow. So, COX-2 products should be used more cautiously in patients with defects in nitric oxide production.