Role of renocortical cyclooxygenase-2 for renal vascular resistance and macula densa control of renin secretion

This study aimed to assess the role of cyclooxygenase-2 (COX-2)-derived pro stanoids for the macula densa control of renal afferent arteriolar resistan ce and for renin secretion. For this purpose, studied were the effects of b locking macula densa salt transport by the loop diuretic bumetanide (100 mu M) on renal perfusate flow and on renin secretion in isolated perfused rats , in which renocortical COX-2 expression was prestimulated in vivo by treat ment with the angiotensin-converting enzyme inhibitor ramipril, with low-sa lt diet, or with a combination of both. These maneuvers stimulated COX-2 ex pression in an order of ramipril + low salt much greater than low salt > ra mipril > controls. Flow rates through isolated kidneys at a constant pressu re of 100 mmHg were dependent on the pretreatment regimen, in the way that they went in parallel with COX-2 expression. The COX-2 inhibitor NS-398 (10 muM) lowered flow rates depending on the COX-2 expression level and was mo st pronounced therefore after pretreatment with low salt + ramipril. NS-398 did not change the increase of flow in response to bumetanide but attenuat ed the stimulation of renin secretion in response to bumetanide in a manner depending on the expression level of COX-2. These findings suggest that in states of increased renocortical expression of COX-2, overall renal vascul ar resistance and the macula densa control of renin secretion become depend ent on COX-2-derived prostanoids.