Lipid emulsion alleviates the vasodilation and mean blood pressure decrease induced by a toxic dose of verapamil in isolated rat aortae and an in vivo rat model.

This study aimed to examine the effects of lipid emulsion on the vasodilation and cardiovascular depression induced by toxic doses of calcium channel blockers. The effects of lipid emulsion on the vasodilation induced by bepridil, verapamil, nifedipine, and diltiazem were investigated in isolated endothelium-denuded rat aortae. The effect of lipid emulsion on the comparable hemodynamic depression induced by the continuous infusion of a toxic dose of either verapamil or diltiazem was examined in an in vivo rat model. The results showed the following decreasing order for the magnitude of lipid emulsion-mediated inhibition of vasodilation: bepridil, verapamil, nifedipine, and diltiazem. Lipid emulsion (0.5-2%) reversed the vasodilation induced by a toxic dose of verapamil, whereas only a higher concentration (2%) reversed the vasodilation induced by a toxic dose of diltiazem. Pretreatment with lipid emulsion alleviated the systolic and mean blood pressure decreases induced by a toxic dose of verapamil, whereas it had no effect on the decrease induced by diltiazem. Taken together, these results suggest that lipid emulsion alleviates the severe vasodilation and systolic blood pressure decrease induced by a toxic dose of verapamil, and this alleviation appears to be associated with the relatively high lipid solubility of verapamil.

Lipid emulsion attenuates apoptosis induced by a toxic dose of bupivacaine in H9c2 rat cardiomyoblast cells.

The goal of this in vitro study was to investigate the effect of lipid emulsion on apoptosis induced by a toxic dose of bupivacaine (BPV) in H9c2 rat cardiomyoblast cell lines. The effect of lipid emulsion on the decreased cell viability and count induced by BPV or mepivacaine (MPV) in the H9c2 cells was assessed using an 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide assay or a cell count assay. The effect of BPV or lipid emulsion combined with BPV on cleaved caspase 3, caspase 8, and Bax in H9c2 cells was investigated using Western blotting. A terminal deoxynucleotidyl transferase dUTP2'-deoxyuridine 5'-triphosphate nick end-labeling (TUNEL) assay was performed to detect apoptosis of H9c2 cells treated with BPV alone or lipid emulsion combined with BPV. The magnitude of lipid emulsion-mediated attenuation of decreased cell viability induced by BPV was higher than that of lipid emulsion-mediated attenuation of decreased cell viability induced by MPV. Lipid emulsion attenuated the increases in cleaved caspase 3, caspase 8 and Bax induced by BPV. Lipid emulsion attenuated the increases in TUNEL-positive cells induced by BPV. These results suggest that lipid emulsion attenuates a toxic dose of BPV-induced apoptosis via inhibition of the extrinsic and intrinsic apoptotic pathways. The protective effect of lipid emulsion may be partially associated with the relatively high lipid solubility of BPV.

Alfentanil attenuates phenylephrine-induced contraction in rat aorta.

BACKGROUND AND OBJECTIVES: Alfentanil was reported to relax the rat aorta by direct action on the vascular smooth muscle. The aims of this in vitro study were to examine the effect of alfentanil on phenylephrine-induced contractions in the rat aorta and to determine the cellular mechanism associated with this process. METHODS: Endothelium-denuded aortic rings were suspended in order to record isometric tension. In the rings with or without 10(-6) mol naloxone or 10(-5) mol verapamil, the concentration-response curves for phenylephrine and potassium chloride were generated in the presence or absence of alfentanil (10(-6), 5 x 10(-5), 10(-4) mol). In the rings exposed to a calcium-free isotonic depolarizing solution, the contractile response induced by the addition of calcium was assessed in the presence or absence of alfentanil (5 x 10(-5), 10(-4) mol). RESULTS: Alfentanil (5 x 10(-5), 10(-4) mol) attenuated (P < 0.05) the phenylephrine-induced contraction in the ring with or without 10(-6) mol naloxone but had no effect on the phenylephrine-induced contraction in the rings pretreated with verapamil. Alfentanil (5 x 10(-5), 10(-4) mol) produced a significant rightward shift (P < 0.01) in the potassium chloride dose-response curve, and attenuated the contractile response (P < 0.001) induced by calcium in the calcium-free isotonic depolarizing solution in a dose-dependent manner. CONCLUSIONS: A supraclinical dose of alfentanil attenuates the phenylephrine-induced contraction via an inhibitory effect on calcium influx by blocking the l-type calcium channels in the rat aortic vascular smooth muscle.

Effect of etomidate on endothelium-dependent relaxation induced by acetylcholine in rat aorta.

The goals of this in vitro study were to investigate effects of etomidate on endothelium-dependent relaxation induced by acetylcholine in rat aorta, and to elucidate the associated cellular mechanism. In endothelium-intact rings precontracted with phenylephrine 10(-6) M, dose-response curves for acetylcholine (10(-9) to 10(-5) M) and calcium ionophore (10(-9) to 10(-6) M) were generated in the presence and absence of etomidate (5 x10(-6) 10(-5) M). In endothelium-intact or -denuded rings precontracted with phenylephrine 10(-6) M, sodium nitroprusside (10(-9) to 10(-6) M) dose-response curves were generated in the presence and absence of etomidate (10(-5)M). Etomidate (5 x10(-6), 10(-5)M) produced a significant rightward shift in the dose-response curves induced by acetylcholine (receptor-mediated endothelium-dependent agonist) and calcium ionophore A23187 (non receptor-mediated endothelium-dependent agonist). Etomidate (10(-5)M) had no effect on sodium nitroprusside (endothelium-independent nitric oxide donor)-induced vasorelaxant response in both endothelium-intact and -denuded rings. These results indicate that etomidate at clinically relevant concentrations attenuates endothelium-dependent relaxation induced by acetylcholine by an acting at a site distal to the endothelial muscarinic receptor, but proximal to guanylate cyclase activation of vascular smooth muscle in rat aorta.