Activation of renal mechanosensitive neurons involves bradykinin, protein kinase C, PGE(2), and substance P

Increased renal pelvic pressure or bradykinin increases afferent renal nerv e activity (ARNA) via PGE(2)-induced release of substance P Protein kinase C (PKC) activation increases ARNA, and PKC inhibition blocks the ARNA respo nse to bradykinin. We now examined whether bradykinin mediates the ARNA res ponse to increased renal pelvic pressure by activating PKC. In anesthetized rats, the ARNA responses to increased renal pelvic pressure were blocked b y renal pelvic perfusion with the bradykinin B-2-receptor antagonist HOE 14 0 and the PKC inhibitor calphostin C by 76 +/- 8% (P < 0.02) and 81 +/- 5% (P < 0.01), respectively. Renal pelvic perfusion with 4 beta-phorbol 12,13- dibutyrate (PDBu) to activate PKC increased ARNA 27 +/- 4% and renal pelvic release of PGE(2) from 500 +/- 59 to 1,113 +/- 183 pg/min and substance P from 10 +/- 2 to 30 +/- 2 pg/min tall P < 0.01). Indomethacin abolished the increases in substance P release and ARNA. The PDBu-mediated increase in A RNA was also abolished by the substance P-receptor antagonist RP 67580. We conclude that bradykinin contributes to the activation of renal pelvic mech anosensitive neurons by activating PKC. PKC increases ARNA via a PGE2-induc ed release of substance P.