BRADYKININ-MEDIATED ACTIVATION OF RENAL SENSORY NEURONS DUE TO PROSTAGLANDIN-DEPENDENT RELEASE OF SUBSTANCE-P

In anesthetized rats, renal pelvic administration of bradykinin result s in a prostaglandin (PG)-dependent increase in afferent renal nerve a ctivity (ARNA). We now measured renal pelvic release of PGE and substa nce P during renal pelvic administration of bradykinin. Bradykinin inc reased ARNA and renal pelvic release of PGE by 497 +/- 252 pg/min and substance P by 10.7 +/- 7.2 pg/min. Renal pelvic perfusion with indome thacin abolished the bradykinin-mediated increase in ARNA and reduced renal pelvic release of PGE and substance P by 76 +/- 11 and 72 +/- 8% , respectively. To examine whether the increased substance P release c ontributed to bradykinin-mediated activation of renal sensory receptor s, renal pelvis was perfused with the substance P-receptor antagonists CP-96,345, CP-99,994, or RP-67580. The ARNA response to bradykinin wa s reduced 73 +/- 11, 55 +/- 12, and 64 +/- 10% by CP-96,345, CP-99,994 , and RP-67580, respectively. The inactive enantiomers CP-96,344 and R P-68651 had no effect. These data suggest that bradykinin increases re nal pelvic release of PGE, which facilitates the release of substance P, which in turn stimulates substance P receptors. Thus the ARNA respo nse to bradykinin is largely mediated by activation of substance P rec eptors.