Mechanism of the ropivacaine-induced increase in intracellular Ca2+ concentration in rat aortic smooth muscle.
BACKGROUND
Ropivacaine is a long-acting local anesthetic with low cardiac toxicity that induces vasoconstriction in vitro and in vivo. Vascular smooth muscle tone is regulated by changes in both intracellular Ca(2+) concentration ([Ca(2+)](i)) and myofilament Ca(2+) sensitivity. Therefore, the aim of this study was to examine the mechanism underlying the increase in [Ca(2+)](i) in ropivacaine-induced vascular contraction.


METHODS
Ropivacaine-induced contractile responses and changes in [Ca(2+)](i) were examined using an isometric force transducer and a fluorometer, respectively.


RESULTS
Ropivacaine induced a biphasic, concentration-dependent change in [Ca(2+)](i) and contractile response in rat aortic smooth muscles: an increase in [Ca(2+)](i) occurred at lower ropivacaine concentrations (3 x 10(-5) to 3 x 10(-4) M) and a decrease was observed at higher concentrations (10(-3) to 3 x 10(-3) M). Contraction and the [Ca(2+)](i) increase induced by ropivacaine were attenuated significantly by a voltage-dependent Ca(2+) channel antagonist, an inositol 1,4,5-triphosphate receptor antagonist and Ca(2+)-free solution (P < 0.01, n = 6).


CONCLUSIONS
Ropivacaine-induced contraction of rat aortic smooth muscle is, in part, regulated by Ca(2+) influx from the extracellular space and Ca(2+) release from the sarcoplasmic reticulum.
Tokinaga
Y
Y
Surgical Operating Center, Wakayama Medical University, Wakayama City, Japan.
Ogawa
K
K
Yu
J
J
Kuriyama
T
T
Minonishi
T
T
Hatano
Y
Y
D000577:Amides / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001011:Aorta; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009529:Nicardipine / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D000077212:Ropivacaine; D014661:Vasoconstriction / Q000187:drug effects*
D000577:Amides; D000779:Anesthetics, Local; D002121:Calcium Channel Blockers; D000077212:Ropivacaine; D009529:Nicardipine; D002118:Calcium