Mechanism of vasodilation by propofol in the rabbit renal artery

Background: Propofol directly inhibits vascular reactivity. How-ever, available information regarding the underlying mechanisms of propofol is poor. Therefore, mechanisms of the underlying relaxant action of propofol were investigated using rabbit renal arteries. Methods: Propofol-induced relaxation of rabbit renal arteries was studied in contracted preparations with 50 mM KCl or 10 μ M histamine. Vessel tension was recorded with a pen recorder. We were interested in determining whether propofol-induced vasodilation is affected by endothelium-denudation, L-NG-nitroarginine methyl ester (L-NAME), tetraethylammonium (TEA), iberiotoxin, glibenclamide, 4-aminopyridine, 7-ethoxyresorufin, caffeic acid, baiclalein, ryanodine, and thapsigargin. Results: Propofol-induced concentration-dependent vasodilation was not affected either by endothelium denudation or by L-NAME during histamine-induced contraction. The relaxing effect of propofol on histamine-induced contraction was inhibited by either TEA, a K ＋ channel inhibitor, or iberiotoxin (100 nM), a selective blocker of the large conductance Ca 2 ＋ -activated K ＋ channel (BKCa channel). In contrast, the relaxing effect of propofol was unaffected by 10 μ M glibenclamide, an ATP-sensitive K ＋ channel blocker, by 5 mM 4-aminopyridine, a blocker of delayed rectifier, by 7-ethoxyresorufin, a cytochrome P450 inhibitor, by 10 μ M caffeic acid and 10 μ M baiclalein, lipooxygenase inhibitors, or by 10 μ M ryanodine and thapsigargin, Ca 2 ＋ store inhibitors. Conclusions: These results suggest that the relaxant effect of propofol may result from activation of BKCa channels by inhibiting voltage-gated Ca 2 ＋ influx in a prolonged manner. (Anesth Pain Med 2011; 6: 336 ∼ 341)