Renal sensory receptor activation causes prostaglandin-dependent release of substance P

Renal mechanoreceptor (MR) activation by increased ureteral pressure (up arrow UP) results in an increase in afferent renal nerve activity (ARNA) that is blocked by substance P receptor blockade and prostaglandin (PG) synthesis inhibition. To examine the interaction between substance P and PGs, the release of substance P and PGE into the renal pelvis was studied before and during renal pelvic perfusion with indomethacin. Before indomethacin, up arrow UP increased ARNA 43 +/- 6% and renal pelvic release of substance P from 11 +/- 3 to 29 +/- 8 pg/min and PGE from 319 +/- 71 to 880 +/- 146 pg/min. Indomethacin. blocked the increases in ARNA and release of substance P and PGE produced by up arrow UP. Time control experiments showed reproducible increases in ARNA and release of substance P and PGE during up arrow UP. Mechanical stimulation of the renal pelvic wall in vitro resulted in an increase in PGE release from 110 +/- 8 to 722 +/- 152 pg/min, which was abolished by indomethacin, suggesting a de novo PGE synthesis. The data suggest that up arrow UP results in a renal pelvic release of PGE, which facilitates the release of substance P and activation of renal pelvic MR.