OBJECTIVE: Palmitoyl-L-carnitine, which accumulates in ischaemic myocardium, may influence the function of vascular endothelium in the ischaemic area. The aim of the study was therefore to examine the effect of palmitoyl-L-carnitine on endothelium dependent relaxations of rabbit thoracic aortas and its effects on the intracellular calcium regulation in cultured bovine aortic endothelial cells (BAEC). METHODS: Isometric contraction experiments on rabbit thoracic aorta were performed to evaluate the effect of palmitoyl-L-carnitine on endothelium dependent relaxation. BAEC were isolated by scraping the internal surface of the aorta from slaughtered cow, and were cultured in Dulbecco's modified Eagle's medium supplemented with fetal calf serum (15% v/v). Cultures used in the present study were from the third to the 12th passage. The cytosolic Ca2+ level in BAEC was monitored by the fura-2 method. RESULTS: Palmitoyl-L-carnitine (1-20 microM) inhibited endothelium dependent relaxation induced by acetylcholine and substance P in a dose dependent manner, while having no effect on resting tension and glyceryl trinitrate induced relaxations. Bradykinin, another endothelium dependent relaxant, induced a biphasic Ca2+ transient in BAEC. Pretreatment of BAEC with palmitoyl-L-carnitine (5-10 microM) inhibited bradykinin induced Ca2+ transients. CONCLUSIONS: The inhibitory effect of palmitoyl-L-carnitine on endothelium dependent relaxation results from the suppression of the intracellular calcium signal transduction in endothelial cells. We speculate that palmitoyl-L-carnitine may be an important mediator of the impaired vascular endothelial function in myocardial ischaemia.
OBJECTIVE:Palmitoyl-L-carnitine, which accumulates in ischaemic myocardium, may influence the function of vascular endothelium in the ischaemic area. The aim of the study was therefore to examine the effect of palmitoyl-L-carnitine on endothelium dependent relaxations of rabbit thoracic aortas and its effects on the intracellular calcium regulation in cultured bovine aortic endothelial cells (BAEC). METHODS: Isometric contraction experiments on rabbit thoracic aorta were performed to evaluate the effect of palmitoyl-L-carnitine on endothelium dependent relaxation. BAEC were isolated by scraping the internal surface of the aorta from slaughtered cow, and were cultured in Dulbecco's modified Eagle's medium supplemented with fetal calf serum (15% v/v). Cultures used in the present study were from the third to the 12th passage. The cytosolic Ca2+ level in BAEC was monitored by the fura-2 method. RESULTS:Palmitoyl-L-carnitine (1-20 microM) inhibited endothelium dependent relaxation induced by acetylcholine and substance P in a dose dependent manner, while having no effect on resting tension and glyceryl trinitrate induced relaxations. Bradykinin, another endothelium dependent relaxant, induced a biphasic Ca2+ transient in BAEC. Pretreatment of BAEC with palmitoyl-L-carnitine (5-10 microM) inhibited bradykinin induced Ca2+ transients. CONCLUSIONS: The inhibitory effect of palmitoyl-L-carnitine on endothelium dependent relaxation results from the suppression of the intracellular calcium signal transduction in endothelial cells. We speculate that palmitoyl-L-carnitine may be an important mediator of the impaired vascular endothelial function in myocardial ischaemia.