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

Abstract

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 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 due to sodium restriction or chronic treatment with angiotensin converting enzyme (ACE) inhibitors showed similar 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.

Recurrent insulin-induced hypoglycemia induces AngII and COX2 leading to renal (pro)renin receptor expression and oxidative stress

“…Also, our results found that the inhibition of AngII and COX2 blocked RIIH-induced PRR expression, which confirmed the essential roles of AngII and COX2 in increasing renal PRR expression during RIIH. Previous studies documented that COX2/PGE2/EP4 pathway is responsible for high PRR expression in the renal medulla during AngII-induced hypertension (Green et al 2012, Wang et al 2014, Yang 2015. However, in the current study, RIIH induced AngII which might activate the COX2/PGE2/EP4 pathway and lead to an increase in expression of PRR in the kidney.…”

Asociación y efectos de interacción en los genes AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R y PTGS2 sobre la hipertensión en población antioqueña

“…De manera similar, los efectos de COX2 (PTGS2) se encuentran relacionados con la regulación de la presión arterial, participando principalmente en la síntesis de la prostaciclina PGI2, un importante vasodilatador, antiagregante plaquetario y estimulador de la diuresis (96,97). Aunque no se ha reportado interacción de PTGS2 con aduccinas, nuestro hallazgo es coincide con reportes previos que han mostrado que la expresión renal de PTGS2 se incrementa en condiciones que llevan a un aumento en la reabsorción de sodio (98,99).…”

Use of Nonsteroidal Anti-Inflammatory Drugs and Risk of Chronic Kidney Disease in Subjects With Hypertension

“…35,36 Third, previous reports have provided supportive evidence that COX-2 plays a role in modulating harmful actions of angiotensin II, consequently impacting the regulation of renal function and blood pressure. 37,38 Fourth, previous studies have demonstrated that NSAIDs could increase plasma asymmetrical dimethylarginine level, indicating NSAIDs' impacts on inhibition of renal COX-2 and consequent cardiovascular dysfunction and renal disease progression. 38,39 For example, Kielstein et al 39 documented that systemic infusion of asymmetrical dimethylarginine reduced renal plasma flow and had considerable effects on systemic vascular resistance.…”