Acute upregulation of COX-2 by renal artery stenosis.

Abstract

This study aimed to characterize the influence of acute renal artery stenosis on cyclooxygenase-2 (COX-2) and renin expression in the juxtaglomerular apparatus. For this purpose, male Sprague-Dawley rats received a left renal artery clip, and COX-2 mRNA, COX-2 immunoreactivity, plasma renin activity, and renin mRNA levels were determined. COX-2 mRNA and COX-2 immunoreactivity in the macula densa region in the clipped kidneys increased as early as 6 h after clipping and reached a maximal expression 1-2 days after clipping. Although values for plasma renin activity were elevated markedly at all time points examined, remaining renin mRNA levels were unchanged after 6 h and then increased to reach a maximum value 1-2 days after clipping. In the contralateral intact kidney, renin mRNA and COX-2 immunoreactivity decreased to approximately 50% of their normal values. To investigate a possible causal relationship between the changes of COX-2 and of renin expression, clipped rats were treated with the COX-2 blocker celecoxib (40 mg. kg(-1). day(-1)). This treatment, however, did not change renin mRNA either in the clipped or in the contralateral intact kidney. Our findings indicate that renal artery stenosis causes ipsilaterally an acute upregulation and contralaterally a downregulation of juxtaglomerular COX-2 expression. The lacking effect of celecoxib on renin gene expression does not support the concept of a direct mediator function of COX-2-derived prostaglandins in the control of renin expression during renal hypoperfusion.