Bradykinin attenuates the [Ca2+](i) response to angiotensin II of renal juxtamedullary efferent arterioles via an EDHF

1 Bradykinin (BK) effect on the [Ca2+](i) response to 1 nM angiotensin II w as examined in muscular juxtamedullary efferent arterioles (EA) of rat kidn ey. 2 BK (10 nM) applied during the angiotensin II-stimulated [Ca2+](i) increas e, induced a [Ca2+](i) drop (73+/-2%). This drop was prevented by de-endoth elialization and suppressed by HOE 140, a B2 receptor antagonist. It was ne ither affected by L-NAME or indomethacin, nor mimicked by sodium nitropruss ide, 8-bromo-cyclic GMP or PGI(2). The BK effect did not occur when the [Ca 2+](i) increase was caused by 100 mM KCl-induced membrane depolarization an d was abolished by 0.1 muM charybdotoxin, a K+ channel blocker. 3 Although proadifen prevented the BK-caused [Ca2+](i) fall, more selective cytochrome P450 inhibitors, 17-octadecynoic acid (50 muM) and 7-ethoxyreso rufin (10 muM) were without effect. 4 Increasing extracellular potassium from 5 to 15 mM during angiotensin II stimulation caused a [Ca2+](i) decrease (26+/-4%) smaller than BK which was charybdotoxin-insensitive. Inhibition of inward rectifying K+ channels by 30 muM BaCl2 and/or of Na+/K+ ATPase by 1 mM ouabain abolished the [Ca2+](i ) decrease elicited by potassium but not by BK. 5 A voltage-operated calcium channel blocker, nifedipine (1 muM) did not pr event the BK effect but reduced the [Ca2+](i) drop. 6 These results indicate that the BK-induced [Ca2+](i) decrease in angioten sin II-stimulated muscular EA is mediated by an EDHF which activates charyb dotoxin-sensitive K+ channels. In these vessels, EDHF seems to be neither a cytochrome P450-derived arachidonic acid metabolite nor K+ itself. The clo sure of voltage-operated calcium channels is not the only cellular mechanis m involved in this EDHF-mediated [Ca2+](i) decrease.