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 prostagland in (PG) synthesis inhibition. To examine the interaction between subst ance P and PGs, the release of substance P and PGE into the renal pelv is was studied before and during renal pelvic perfusion with indometha cin. Before indomethacin, up arrow UP increased ARNA 43 +/- 6% and ren al 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 i ncreases in ARNA and release of substance P and PGE produced by up arr ow UP. Time control experiments showed reproducible increases in ARNA and release of substance P and PGE during up arrow UP. Mechanical stim ulation of the renal pelvic wall in vitro resulted in an increase in P GE release from 110 +/- 8 to 722 +/- 152 pg/min, which was abolished b y indomethacin, suggesting a de novo PGE synthesis. The data suggest t hat up arrow UP results in a renal pelvic release of PGE, which facili tates the release of substance P and activation of renal pelvic MR.