Angiotensin II attenuates renal cortical cyclooxygenase-2 expression

We have previously shown that in rat renal cortex, cyclooxygenase-2 (COX-2) expression is localized to cTALH cells in the region of the macula densa, and that dietary salt restriction increases COX-2 expression. Administratio n of the angiotensin converting inhibitor, captopril, further increased COX -2, mRNA and renal cortical COX-2 immunoreactivity, with the most pronounce d expression in the macula densa. Administration of an AT1 receptor antagon ist, losartan, also significantly increased cortical COX-2 mRNA expression and COX-2 immunoreactivity. Mutant mice homozygous for both Agtr1a and Agtr 1b null mutations (Agtr1a(-/-),Agtr1b(-/-)) demonstrated large increases in immunoreactive COX-2 expression in the cTALH/macula densa. To determine wh ether increased COX-2 expression in response to ACE inhibition mediated inc reases in renin production, rats were treated with captopril for one week w ith or without the specific COX-2 inhibitor, SC58236. Plasma renin activity increased significantly in the captropril group, and this increase was sig nificantly inhibited by simultaneous treatment with SC58236. Thus, these st udies indicated that angiotensin II inhibitors augment upregulation of rena l cortical COX-2 in states of volume depletion, suggesting that negative fe edback by the renin-angiotensin system modulates renal cortical COX-2 expre ssion and that COX-2 is a mediator of increased renin production in respons e to inhibition of angiotension II production.