Bradykinin attenuates the [Ca super(2+)] sub(i) response to angiotensin II of renal juxtamedullary efferent arterioles via an EDHF

Bradykinin (BK) effect on the [Ca super(2+)] sub(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 [Ca super(2+)] sub(i) increase, induced a [Ca super(2+)] sub(i) drop (73 plus or minus 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 PGI sub(2). The BK effect did not occur when the [Ca super(2+)] sub(i) increase was caused by 100 mM KCl-induced membrane depolarization and was abolished by 0.1 mu M charybdotoxin, a K super(+) channel blocker. Although proadifen prevented the BK-caused [Ca super(2+)] sub(i) fall, more selective cytochrome P450 inhibitors, 17-octadecynoic acid (50 mu M) and 7-ethoxyresorufin (10 mu M) were without effect. Increasing extracellular potassium from 5 to 15 mM during angiotensin II stimulation caused a [Ca super(2+)] sub(i) decrease (26 plus or minus 4%) smaller than BK which was charybdotoxin-insensitive. Inhibition of inward rectifying K super(+) channels by 30 mu M BaCl sub(2) and/or of Na super(+)/K super(+) ATPase by 1 mM ouabain abolished the [Ca super(2+)] sub(i) decrease elicited by potassium but not by BK. A voltage-operated calcium channel blocker, nifedipine (1 mu M) did not prevent the BK effect but reduced the [Ca super(2+)] sub(i) drop. These results indicate that the BK-induced [Ca super(2+)] sub(i) decrease in angiotensin II-stimulated muscular EA is mediated by an EDHF which activates charybdotoxin-sensitive K super(+) channels. In these vessels, EDHF seems to be neither a cytochrome P450-derived arachidonic acid metabolite nor K super(+) itself. The closure of voltage-operated calcium channels is not the only cellular mechanism involved in this EDHF-mediated [Ca super(2+)] sub(i) decrease.