Involvement of protein kinase C in the supersensitivity to 5-HT caused by oxidized low-density lipoproteins

• Published in: Life sciences (1973) 1997, Vol.61 (14), p.1331-1339
• Main Authors: Encabo, Araceli, Ferrer, Mercedes, Conde, María Victoria, Porres, Amelia, Gómez-Gerique, Juan Antonio, Marín, Jesús, Balfagón, Gloria
• Format: Article
• Language: English
• Subjects: Acetylcholine - pharmacology; Animals; Aorta, Thoracic - drug effects; Aorta, Thoracic - physiology; endothelium-dependent relaxation; Enzyme Inhibitors - pharmacology; In Vitro Techniques; Lipoproteins, LDL - metabolism; lyso-phosphatidylcholines; Male; Muscle Contraction - drug effects; Muscle Relaxation - drug effects; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - physiology; native low-density lipoprotein; oxidized low-density lipoprotein; Phorbol 12,13-Dibutyrate - pharmacology; Potassium - pharmacology; protein kinase C; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - metabolism; rabbit aorta; Rabbits; serotonin; Serotonin - pharmacology; Staurosporine - pharmacology
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/S0024-3205(97)00678-4

The effect of native (n-LDL) and oxidized (ox-LDL) low-density lipoproteins and lysophosphatidylcholines (LPCs) on: (1) vasodilator responses induced by acetylcholine (ACh) in intact rabbit aorta segments, and (2) vasoconstrictor responses to serotonin (5-HT), and potassium (K +) in endothelium denuded segments was investigated. In intact vessels, 100 μg ml ox-LDL did not modify ACh-induced relaxation, while it was diminished by 300 μg ml ox-LDL and abolished by 50 μM LPCs. In contrast, this relaxation was unaltered by n-LDL (100 or 300 μg ml ). In deendothelialized arteries, 100 and 300 μg ml n-LDL as well as 50 μM LPCs did not modify the contractions induced by 5-HT or K +, while 100 or 300 μg ml ox-LDL increased the 5-HT-induced contraction, without altering those induced by 75 mM K +. Incubation with 100 or 300 μg ml ox-LDL increased the contractile response to the protein kinase C (PKC) activator phorbol 12,13-dibutyrate (PDB) (0.1–1 μM) in a concentration-dependent manner, which was blocked by staurosporine (0.1 μM), and unaltered by (50 μM) calphostin C or (50 μM) chelerythrine, the three are PKC inhibitors. Preincubation with 0.05 μM PDB increased the contraction elicited by 5-HT, while staurosporine decreased the PDB-induced contraction, and prevented the 5-HT response increase caused by 300 μg ml ox-LDL. These results suggest that only ox-LDL reduces endothelium-dependent relaxation and elicits PKC activation, and that this activation mediates, at least in part, the vasoconstrictor response to 5-HT.