Etomidate attenuates phenylephrine-induced contraction in isolated rat aorta

Abstract

Purpose: A previous study has shown that etomidate inhibits the angiotensin II-induced calcium influx in rat aortic smooth muscle cells. The goals of our current in vitro study were to investigate the effect of etomidate on phenylephrine-induced contraction in rat aorta, and to elucidate the associated signalling pathway.Methods: Endothelium-denuded aortic rings were suspended for isometric tension recording. Concentration-response curves for phenylephrine (10 -9 to 10 -6 M), 5-hydroxytryptamine (10 -7 to 10 -4 M) and potassium chloride (10 to 60 mM) were generated in the presence and absence of etomidate (5 × 10 M). In the rings exposed to calcium-free isotonic depolarizing solution, the contractile response induced by the addition of calcium was assessed in the presence and absence of etomidate (5 × 10 -5 M).Results: Etomidate (5 × 10 -5 M) produced a significant rightward shift in the concentration-response curves for phenylephrine, 5-hydroxytryptamine and potassium chloride. Etomidate (5 × 10 -5 M) did not alter phenylephrine-induced contraction in the rings pretreated with verapamil. Etomidate (5 × 10 -5 M) significantly attenuated the contractile response induced by the addition of calcium in the calcium-free isotonic depolarizing solution. Conclusion:The results suggest that etomidate, which exceeds the clinically relevant concentration, attenuates the phenylephrine-induced contraction by having an inhibitory effect on the calcium influx by blocking the L-type calcium channels in the rat aortic vascular smooth muscle. Objectif

Bupivacaine-induced Vasodilation Is Mediated by Decreased Calcium Sensitization in Isolated Endothelium-denuded Rat Aortas Precontracted with Phenylephrine

“…In agreement with previous findings that verapamil attenuates phenylephrine-induced contraction and that norepinephrine-induced contraction involves calcium influx via both voltage- and receptor-operated calcium channels, verapamil attenuated phenylephrine-induced contraction (Fig. 4), suggesting that phenylephrine-induced contraction appears to involve partial activation of voltage-operated calcium channels [12,23]. In addition, norepinephrine-induced contraction involves the opening of verapamil-sensitive L-type calcium channels [22].…”

“…Hyperpolarization in the membrane potential of vascular smooth muscle induced by the activation of various potassium channels, including voltage-dependent, calcium-activated, inward-rectifying, and adenosine triphosphate-sensitive potassium channels, produces vasodilation via the inhibition of calcium influx [11]. In addition, etomidate and alfentanil attenuate phenylephrine-induced contraction via an inhibitory effect on voltage-operated calcium channels [12,13]. Rho-kinase and protein kinase C are involved in the increased calcium sensitization, which lead to local anesthetic-induced vasoconstriction, whereas decreased calcium sensitization attenuates local anesthetic-induced vasoconstriction, which may be involved in vasodilation [6,14,15].…”

Protective effect of crocin on diazinon induced vascular toxicity in subchronic exposure in rat aortaex-vivo

“…So, the decreased effect of DZN on KCl induced contraction may be related to the inhibitory effect of DZN on voltage dependent calcium channels. Furthermore PE (an a1-receptor agonist) -induced contraction involves receptor-operated calcium and voltageoperated calcium channels, whereas KCl-induced contraction is mediated by voltage-operated calcium channels (Karaki et al, 1997;Shin et al, 2005). Thus, inhibitory effect of DZN on KCl-and PE-induced contraction seems to be associated with inhibition of voltage-operated calcium channels, leading to decreased intracellular calcium concentration.…”

Levobupivacaine-induced contraction of isolated rat aorta is calcium dependent

“…This solution was then replaced by a calcium-free isotonic depolarizing solution containing a high concentration of K + (100 mmol/L KCl); and SKF-96365 was then added directly to this solution 15 min before calcium-induced contraction. Finally, calcium was added cumulatively to achieve a final bath concentration of 0.5-3 mmol/L (Shin et al 2005).…”