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

• Published in: British journal of pharmacology 2001-02, Vol.132 (3), p.749-759
• Main Authors: Marchetti, Jeannine, Praddaude, Françoise, Rajerison, Rabary, Ader, Jean‐Louis, Alhenc‐Gelas, François
• Format: Article
• Language: English
• Subjects: [Ca2+]i; Biological and medical sciences; Blood vessels and receptors; bradykinin; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; cytochrome P450; EDHF; Fundamental and applied biological sciences. Psychology; Glomerular efferent arterioles; K+ channels; potassium; Vertebrates: cardiovascular system; Vertebrates: nervous system and sense organs; Vertebrates: urinary system; voltage‐operated calcium channels
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0703851

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