Investigation of the mechanism of action of propofol-induced vasodilation in human internal mammary artery: Role of potassium channels

Propofol is an intravenous anesthetic that can be used for the induction and maintaining of anesthesia. The aim of this study was to investigate the mechanism of the vasodilator action of propofol in the human internal mammary artery (IMA). The IMA rings were suspended in the isolated organ bath and the changes in tension were recorded isometrically. Potassium chloride (KCl) and phenylephrine were added to organ baths to form precontraction. Propofol (1 μM, 10 μM, 100 μM) was added cumulatively when the precontractions were stable. The antagonistic effect of propofol was investigated on the contractions induced by KCl (45 mM), phenylephrine (1 μM), 5-hydroxytryptamine (5-HT, 30 μM) and CaCl2 (10-2-10-5 M). Propofol-induced relaxations were also tested in the presence of the large conductance Ca+2-activated K+ channel inhibitors, tetraethylammonium (TEA) or iberiotoxin; ATP-sensitive K+ channel inhibitor, glibenclamide; voltage-sensitive K+ channel inhibitor, 4-aminopyridine; inward rectifier K+ channel inhibitor, barium chloride (BaCl2); cyclooxygenase inhibitor, indomethacin; and nitric oxide synthase inhibitor, nitro-L-arginine methyl ester (L-NAME). Preincubation with propofol (1 μM, 10 μM, 100 μM) did not affect the basal tone. Propofol (10 μM, 100 μM) inhibited the contractions induced by KCl, phenylephrine, 5-HT, and CaCl2 (p<0.01). Propofol-induced relaxations were not affected by 4-aminopyridine, glibenclamide, BaCl2, indomethacin, and L-NAME while iberiotoxin or TEA inhibited the relaxations significantly (p<0.001). Propofol induced the vascular smooth muscle dependent and endothelium independent relaxation in IMA. The results demonstrate that the mechanism of vasodilator effect of propofol may be related to Ca+2-activated K+ channel activation. Keywords: BKCa, Internal mammary artery, Potassium channels, Propofol