title: The complex interplay between cyclooxygenase-2 and angiotensin II in regulating kidney function.
abstract: OBJECTIVE
  Cyclooxygenase-2 (COX-2) plays a critical role in modulating deleterious actions of angiotensin II (Ang II) where there is an inappropriate activation of the renin-angiotensin system (RAS). This review discusses the recent developments regarding the complex interactions by which COX-2 modulates the impact of an activated RAS on kidney function and blood pressure.
  
  
  RESULTS
  Normal rats with increased COX-2 activity but with different intrarenal Ang II activity because of sodium restriction or chronic treatment with angiotensin-converting enzyme (ACE) inhibitors showed similar renal hemodynamic responses to COX-2-selective inhibition (nimesulide) indicating independence from the intrarenal Ang II activity. COX-2-dependent maintenance of medullary blood flow was consistent and not dependent on dietary salt or ACE inhibition. In contrast, COX-2 influences on sodium excretion were contingent on the prevailing RAS activity. In chronic hypertensive models, COX-2 inhibition elicited similar reductions in kidney function, but COX-2 metabolites contribute to rather than ameliorate the hypertension.
  
  
  CONCLUSIONS
  The maintenance of renal hemodynamics reflects direct and opposing effects of Ang II and COX-2 metabolites. The antagonism in water and electrolyte reabsorption is dependent on the prevailing intrarenal Ang II activity. The recent functional experiments demonstrate a beneficial modulation of Ang II by COX-2 except in the presence of inflammation promoted by hypertension, hyperglycemia, and oxidative stress.
authors.affiliation: Department of Physiology and Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, Louisiana 70112, USA.
authors.forename: Torrance
authors.initials: T
authors.lastname: Green
authors.forename: Alexis A
authors.initials: AA
authors.lastname: Gonzalez
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Mitchell
authors.forename: L Gabriel
authors.initials: LG
authors.lastname: Navar
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000201:enzymology* / Q000209:etiology / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D007674:Kidney Diseases / Q000150:complications / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D012084:Renin-Angiotensin System / Q000187:drug effects; D015398:Signal Transduction
chemical_list: D000959:Antihypertensive Agents; D052246:Cyclooxygenase 2 Inhibitors; D000804:Angiotensin II; D051546:Cyclooxygenase 2
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