The complex interplay between cyclooxygenase-2 and angiotensin II in regulating kidney function.

Green T, Gonzalez AA, Mitchell KD, Navar LG.


PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.

Más información

Título de la Revista: Current Opinion in Nephrology and Hypertension
Volumen: 21
Número: 1
Fecha de publicación: 2012
Página de inicio: 7
Página final: 14
Notas: ISI