Cyclooxygenase-2 involved in stimulation of renal mechanosensitive neurons.
Stretching of the renal pelvic wall activates renal mechanosensitive neurons, resulting in an increase in afferent renal nerve activity (ARNA). Prostaglandin (PG)E(2) plays a crucial role in the activation of renal mechanosensitive neurons through facilitation of the release of substance P from the sensory neurons in the renal pelvic wall. Because wall stretch may induce cyclooxygenase-2 activity, we examined whether cyclooxygenase-2 was expressed in the renal pelvic wall and whether activation of cyclooxygenase-2 contributed 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 pressure in anesthetized surgically operated rats. In anesthetized rats, an increase in renal pelvic pressure increased ARNA by 40+/-2% and increased renal 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-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5H)-furanone reduced the increases in ARNA and PGE(2) by 43+/-5% and 47+/-8%, respectively. We conclude that cyclooxygenase-2 is expressed in the renal pelvic wall and that the activation of cyclooxygenase-2 contributes to the stimulation of renal mechanosensitive neurons in the pelvic wall.
Kopp
U C
UC
Department of Internal Medicine, Department of Veterans Affairs Medical Center and University of Iowa College of Medicine, Iowa City 52242, USA. ukopp@blue.weeg.uiowa.edu
Cicha
M Z
MZ
Smith
L A
LA
Haeggström
J Z
JZ
Samuelsson
B
B
Hökfelt
T
T
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D017308:Etodolac / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D007682:Kidney Pelvis / Q000294:innervation*; D008297:Male; D008465:Mechanoreceptors / Q000502:physiology; D009475:Neurons, Afferent / Q000201:enzymology*; D011312:Pressure; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D012333:RNA, Messenger; D017308:Etodolac; D012964:Sodium; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone