Propofol Causes Sustained Ca2+ Elevation in Endothelial Cells by Stimulating Ryanodine Receptor and Suppressing Plasmalemmal Ca2+ Pump

Abstract

Propofol, a general anesthetic administered intravenously, may cause pain at the injection site. The pain is in part due to irritation of vascular endothelial cells. We here investigated the effects of propofol on Ca 2+ transport and pain mediator release in human umbilical vein endothelial cells (EA.hy926). Propofol mobilized Ca 2+ from cyclopiazonic acid (CPA)-dischargeable pool but did not cause Ca 2+ release from the lysosomal Ca 2+ stores. Propofol-elicited Ca 2+ release was suppressed by 100 mM ryanodine, suggesting the participation of ryanodine receptor channels. Propofol did not affect ATP-triggered Ca 2+ release but abolished the Ca 2+ influx triggered by ATP; in addition, propofol also suppressed store-operated Ca 2+ entry elicited by CPA. Ca 2+ clearance during CPA-induced Ca 2+ discharge was unaffected by a low Na + (50 mM) extracellular solution, but strongly suppressed by 5 mM La 3+ (an inhibitor of plasmalemmal Ca 2+ pump), suggesting Ca 2+ extrusion was predominantly through the plasmalemmal Ca 2+ pump. Propofol mimicked the effect of La 3+ in suppressing Ca 2+ clearance. Propofol also stimulated release of pain mediators, namely, reactive oxygen species and bradykinin. Our data suggest propofol elicited Ca 2+ release and repressed Ca 2+ clearance, causing a sustained cytosolic [Ca 2+ ]i elevation. The latter may cause reactive oxygen species and bradykinin release, resulting in pain.

Quaternary amines exert anti-myocardial ischemia effects via regulation of energy metabolism and oxygen free radicals in myocardial cells in acute myocardial infarction rats

“…Thromboxane A2 produced by platelets is metabolized to TXB2 which exerts a contractile effect on vascular smooth muscle. Vascular endothelial cells produce PG12 through synthesis or release, and it inhibits the proliferation of smooth muscle cells via anticoagulation [16]. In pharmacology, quaternary amine inhibits myocardial lipid peroxidation due to its antioxidant properties, thereby reducing oxygen free radical damage to myocardial cells.…”