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.
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.
Authors: Erin M Stitt-Cavanagh; Wissam H Faour; Kaede Takami; Anthony Carter; Barbara Vanderhyden; Youfei Guan; Andre Schneider; Matthew D Breyer; Christopher R J Kennedy Journal: J Am Soc Nephrol Date: 2010-07-29 Impact factor: 10.121
Authors: Jie Zhang; Helena Y Qu; Jiangping Song; Jin Wei; Shan Jiang; Lei Wang; Liqing Wang; Jacentha Buggs; Ruisheng Liu Journal: Physiol Genomics Date: 2017-08-25 Impact factor: 3.107