Prostaglandins are involved in the stimulation of renin gene expression in 2 kidney-1 clip rats

Abstract

This study was done to obtain information about a possible involvement of prostaglandins in the renal baroreceptor mechanism regulating renin secretion and renin gene expression. To this end the effect of the cyclooxygenase inhibition was examined on renin secretion and on renal renin gene expression in 2 kidney-1 clip rats. The influences of the cyclooxygenase inhibitors indomethacin (2mg/kg twice a day) and meclofenamate (8 mg/kg twice a day) on renal renin m-RNA levels, on plasma renin activity (PRA) and on blood pressure were measured 2 days after clipping the left renal arteries of male Sprague-Dawley rats with 0.2 mm clips. In sham-clipped animals, indomethacin and meclofenamate had no significant effect on basal PRA and renin m-RNA levels. In vehicle-treated animals unilateral renal artery clipping increased blood pressure from 120±4.1 to 150±6.1 mmHg, increased PR6A from 7.4±1.6 to 27.6±3.8 as expressed in nanograms of angiotensin I per hour per millilitre, increased renin m-RNA levels of clipped kidneys from 105±5.9% of standard to 482.6±56% of standard and decreased renin m-RNA levels of contralateral kidneys from 116±9.7% of standard to 34±9.0% of standard. While blood pressure, PRA and renin m-RNA levels of the contralateral kidneys were virtually unchanged by the cyclooxygenase inhibitors indomethacin and meclofenamate, renin gene expression in the clipped kidney was markedly influenced by inhibition of prostaglandin synthesis. Both cyclooxygenase inhibitors attenuated the increase of renin m-RNA levels in response to clipped to 280±26% of standard and 261±35% of standard after application of indomethacin or meclofenamate. These findings suggest that intact prostaglandin formation is at least partially required for the stimulatory effect of low renal perfusion pressure on renin gene expression.