Cyclooxygenase-2 involved in stimulation of renal mechanosensitive neurons

Stretching of the renal pelvic wall activates renal mechanosensitive neuron s, resulting in an increase in afferent renal nerve activity (ARNA). Prosta glandin (PG)E-2 plays a crucial role in the activation of renal mechanosens itive neurons through facilitation of the release of substance P from the s ensory neurons in the renal pelvic wall. Because wall stretch may induce cy clooxygenase-2 activity, we examined whether cyclooxygenase-2 was expressed in the renal pelvic wall and whether activation of cyclooxygenase-2 contri buted to the ARNA response produced through increased renal pelvic pressure . In situ hybridization showed a strong cyclooxygenase-2 mRNA signal in the papilla and subepithelial layer of the renal pelvic wall from time control kidneys and from kidneys exposed to 15 minutes of increased renal pelvic p ressure in anesthetized surgically operated rats. In anesthetized rats, an increase in renal pelvic pressure increased ARNA by 40+/-2% and increased r enal pelvic release of PGE(2) from 289+/-46 to 1379+/-182 pg/min (P<0.01). Renal pelvic perfusion with the cyclooxygenase-2 inhibitor etodolac reduced the increases in ARNA and PGE(2) by 66+/-7% and 55+/-13%, respectively (P< 0.01). Likewise, the cyclooxygenase-2 inhibitor 5,5-dimethyl-3-(3-fluorophe nyl)-4-(4-methylsulfonyl)phenyl-2(5H)-furanone reduced the increases in ARN A and PGE(2) by 43+/-5% and 47+/-8%, respectively. We conclude that cycloox ygenase-2 is expressed in the renal pelvic wall and that the activation of cyclooxygenase-2 contributes to the stimulation of renal mechanosensitive n eurons in the pelvic wall.