Mepivacaine-Induced Intracellular Calcium Increase Appears To Be Mediated Primarily By Calcium Influx In Rat Aorta Without Endothelium

Background: Mepivacaine induces contraction or decreased blood flow both in vivo and in vitro. Vasoconstriction is associated with an increase in the intracellular calcium concentration ([Ca2+](i)). However, the mechanism responsible for the mepivacaine-evoked [Ca2+](i) increase remains to be determined. Therefore, the objective of this in vitro study was to examine the mechanism responsible for the mepivacaine-evoked [Ca2+](i) increment in isolated rat aorta.Methods: Isometric tension was measured in isolated rat aorta without endothelium. In addition, fura-2 loaded aortic muscle strips were illuminated alternately (48 Hz) at two excitation wavelengths (340 and 380 nm). The ratio of F340 to F380 (F340/ F380) was regarded as an amount of [Ca2+](i). We investigated the effects of nifedipine, 2-aminoethoxydiphenylborate (2-APB), gadolinium chloride hexahydrate (Gd3+), low calcium level and Krebs solution without calcium on the mepivacaine-evoked contraction in isolated rat aorta and on the mepivacaine-evoked [Ca2+] i increment in fura-2 loaded aortic strips. We assessed the effect of verapamil on the mepivacaine-evoked [Ca2+](i) increment.Results: Mepivacaine produced vasoconstriction and increased [Ca2+](i). Nifedipine, 2-APB and low calcium attenuated vasoconstriction and the [Ca2+](i) increase evoked by mepivacaine. Verapamil attenuated the mepivacaine-induced [Ca2+](i) increment. Calcium-free solution almost abolished mepivacaine-induced contraction and strongly attenuated the mepivacaineinduced [Ca2+](i)increase. Gd3+ had no effect on either vasoconstriction or the [Ca2+](i) increment evoked by mepivacaine.Conclusions: The mepivacaine-evoked [Ca2+](i) increment, which contributes to mepivacaine-evoked contraction, appears to be mediated mainly by calcium influx and partially by calcium released from the sarcoplasmic reticulum.