Role of macula densa cyclooxygenase-2 in renovascular hypertension.

Upregulation of the inducible cyclooxygenase (COX-2) in the macula densa accompanies the activation of the juxtaglomerular apparatus in many high-renin conditions. The functional role of COX-2 in these disease states is poorly understood. We tested whether COX-2 is required to increase renin in renovascular hypertension. Rats with established two-kidney, one-clip (2K1C) hypertension were treated for 2 wk with two different inhibitors of COX-2, NS-398 and rofecoxib, respectively. Hypertension in 2K1C rats was not affected or slightly enhanced by COX-2 inhibition, as measured intra-arterially in conscious animals. The increase in plasma renin activity was also unchanged by both rofecoxib and NS-398. The number of glomeruli with a renin-positive juxtaglomerular apparatus was elevated in clipped kidneys and decreased in contralateral kidneys of 2K1C rats. This pattern was unaltered by COX-2 inhibition. To test the effects of COX-2 blockade on a primarily macula densa-mediated stimulus, we studied salt depletion for comparison. A low-salt diet induced a significant increase in plasma renin activity, which was partially inhibited by treatment with NS-398. We conclude that inhibition of COX-2 in established renovascular hypertension does not affect renin synthesis or release. Thus either COX-2 is not necessary for the macula densa mechanism or the macula densa is not important for maintaining high renin in renovascular hypertension.