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

Bradykinin (BK) effect on the [Ca2+]i response to 1 nM angiotensin II was examined in muscular juxtamedullary efferent arterioles (EA) of rat kidney. BK (10 nM) applied during the angiotensin II-stimulated [Ca2+]i increase, induced a [Ca2+]i drop (73±2%). This drop was prevented by de-endothelialization and suppressed by HOE 140, a B2 receptor antagonist. It was neither affected by L-NAME or indomethacin, nor mimicked by sodium nitroprusside, 8-bromo-cyclic GMP or PGI2. The BK effect did not occur when the [Ca2+]i increase was caused by 100 mM KCl-induced membrane depolarization and was abolished by 0.1 μM charybdotoxin, a K+ channel blocker. Although proadifen prevented the BK-caused [Ca2+]i fall, more selective cytochrome P450 inhibitors, 17-octadecynoic acid (50 μM) and 7-ethoxyresorufin (10 μM) were without effect. 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 μM BaCl2 and/or of Na+/K+ ATPase by 1 mM ouabain abolished the [Ca2+]i decrease elicited by potassium but not by BK. A voltage-operated calcium channel blocker, nifedipine (1 μM) did not prevent the BK effect but reduced the [Ca2+]i drop. These results indicate that the BK-induced [Ca2+]i decrease in angiotensin II-stimulated muscular EA is mediated by an EDHF which activates charybdotoxin-sensitive K+ channels. In these vessels, EDHF seems to be neither a cytochrome P450-derived arachidonic acid metabolite nor K+ itself. The closure of voltage-operated calcium channels is not the only cellular mechanism involved in this EDHF-mediated [Ca2+]i decrease. British Journal of Pharmacology (2001) 132, 749–759; doi:10.1038/sj.bjp.0703851