Article date: February 2001
By: Jeannine Marchetti, Françoise Praddaude, Rabary Rajerison, Jean‐Louis Ader, François Alhenc‐Gelas in Volume 132, Issue 3, pages 749-759
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.
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
DOI: 10.1038/sj.bjp.0703851
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