Renal sensory receptor activation causes prostaglandin-dependent release of substance P.
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Renal mechanoreceptor (MR) activation by increased ureteral pressure (increases 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, increases 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 increases UP. Time control experiments showed reproducible increases in ARNA and release of substance P and PGE during increases 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 increases UP results in a renal pelvic release of PGE, which facilitates the release of substance P and activation of renal pelvic MR.