Bradykinin attenuates the [Ca(2+)](i) response to angiotensin II of renal juxtamedullary efferent arterioles via an EDHF.
1. Bradykinin (BK) effect on the [Ca(2+)](i) response to 1 nM angiotensin II was examined in muscular juxtamedullary efferent arterioles (EA) of rat kidney. 2. BK (10 nM) applied during the angiotensin II-stimulated [Ca(2+)](i) increase, induced a [Ca(2+)](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 PGI(2). The BK effect did not occur when the [Ca(2+)](i) increase was caused by 100 mM KCl-induced membrane depolarization and was abolished by 0.1 microM charybdotoxin, a K(+) channel blocker. 3. Although proadifen prevented the BK-caused [Ca(2+)](i) fall, more selective cytochrome P450 inhibitors, 17-octadecynoic acid (50 microM) and 7-ethoxyresorufin (10 microM) were without effect. 4. Increasing extracellular potassium from 5 to 15 mM during angiotensin II stimulation caused a [Ca(2+)](i) decrease (26+/-4%) smaller than BK which was charybdotoxin-insensitive. Inhibition of inward rectifying K(+) channels by 30 microM BaCl(2) and/or of Na(+)/K(+) ATPase by 1 mM ouabain abolished the [Ca(2+)](i) decrease elicited by potassium but not by BK. 5. A voltage-operated calcium channel blocker, nifedipine (1 microM) did not prevent the BK effect but reduced the [Ca(2+)](i) drop. 6. These results indicate that the BK-induced [Ca(2+)](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 [Ca(2+)](i) decrease.
Marchetti
J
J
Vascular Physiology and Pathology Laboratory, Inserm U367, 17 rue du Fer à Moulin, 75005 Paris, France. marchett@ifm.inserm.fr
Praddaude
F
F
Rajerison
R
R
Ader
J L
JL
Alhenc-Gelas
F
F
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000378:metabolism; D001685:Biological Factors / Q000378:metabolism*; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors; D004347:Drug Interactions; D011464:Epoprostenol / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D001685:Biological Factors; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D065607:Cytochrome P-450 Enzyme Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C067410:endothelium-dependent hyperpolarization factor; D000804:Angiotensin II; D009569:Nitric Oxide; D011189:Potassium Chloride; D011464:Epoprostenol; D009543:Nifedipine; D001920:Bradykinin; D002118:Calcium