Lipid emulsion inhibits the vasodilation induced by a toxic dose of amlodipine in isolated rat aortae

Abstract

The goal of this study was to examine the effect of lipid emulsion on the vasodilation induced in isolated endothelium-denuded rat aortae by a toxic dose of amlodipine. We examined the effects of lipid emulsion and verapamil on amlodipine-induced vasodilation. We also examined the effects of a mixture of lipid emulsion and amlodipine, as well as the centrifuged aqueous extract (CAE) obtained by ultracentrifuging such a mixture and then removing the upper lipid layer, on amlodipine-induced vasodilation. The effect of lipid emulsion on the amlodipine concentration was examined. Lipid emulsion attenuated amlodipine-induced vasodilation in isolated aortae. Both CAE and lipid emulsion containing amlodipine inhibited amlodipine-induced vasodilation. However, there was no significant difference in amlodipine-induced vasodilation between aortae treated with CAE and those treated with lipid emulsion containing amlodipine. Verapamil inhibited amlodipine-induced vasodilation. Lipid emulsion decreased the concentration of amlodipine. Lipid emulsion attenuated the vasodilation induced by a toxic amlodipine dose in NaF-precontracted aortae. The data show that lipid emulsion inhibited the vasodilation induced by a toxic amlodipine dose in isolated rat aortae by reducing the concentration of amlodipine. Amlodipine-induced vasodilation seems to be mediated mainly by blockade of L-type calcium channels and partially by inhibition of the Rho-kinase pathway.

Lipid emulsion attenuates extrinsic apoptosis induced by amlodipine toxicity in rat cardiomyoblasts

“…Studies have shown that lipid emulsion reduces the concentration of drugs with a high lipid solubility (log [octanol/water] partition coefficient: >2), such as bupivacaine, verapamil, and amlodipine, by sequestrating drug molecules on the lipid phase of the emulsion. 7,8,24 Consistent with these findings of previous studies, lipid emulsion-mediated slight reduction in amlodipine concentration in this study might have partially contributed to the inhibition of amlodipine-induced decrease in cell viability. 7,8,24…”

“…7,8,24 Consistent with these findings of previous studies, lipid emulsion-mediated slight reduction in amlodipine concentration in this study might have partially contributed to the inhibition of amlodipine-induced decrease in cell viability. 7,8,24…”

“…Amlodipine (10 −5 M) was emulsified with lipid emulsion (Intralipid: 0%, 0.125%, and 0.25%) in Krebs solution, using a rotator for 30 min, as described previously. 7,8 To determine the concentration of amlodipine released from the samples, the emulsified samples were centrifuged at 75,000 × g for 40 min. The concentration of amlodipine in the aqueous phase (equivalent to centrifuged aqueous extract) was measured by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF MS; Waters, Milford, MA, USA), using an Acquity UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 μm; Waters).…”

“…6 In vitro studies have suggested that lipid emulsion inhibits severe vasodilation induced by calcium channel blockers, including amlodipine, bepridil, and verapamil, at toxic doses. 7,8 However, some case reports have suggested that lipid emulsion may have no effect on cardiovascular collapse induced by amlodipine toxicity. 9,10 Overall, the conclusions on lipid emulsion treatment for amlodipine toxicity are conflicting.…”

Nitric oxide-dependent vasodilation induced by minoxidil in isolated rat aorta

“…Minoxidil (10 -4 M) in Krebs solution was mixed with Intralipid (0.5, 2 and 5%) using a rotator for 30 min to emulsify the minoxidil and lipid emulsion, as previously described (Ok et al 2019a). After centrifugation at 75,000 × g for 40 min, the minoxidil concentration in the aqueous phase was measured by ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF MS; Waters, Milford, MA, USA) with multiple reaction monitoring (MRM).…”