Relaxant and antiadrenergic effects of ranolazine in human saphenous vein
OBJECTIVES: Ranolazine improves vascular function in animal models. We evaluate the effects of ranolazine on vascular function and adrenergic response in human saphenous vein.; METHODS: Rings from 53 patients undergoing coronary artery bypass grafting were mounted in organ baths. Concentration-respo...
| Authors: | , , , , , , , |
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| Format: | article |
| Status: | Published version |
| Publication Date: | 2020 |
| Country: | España |
| Institution: | INCLIVA |
| Repository: | r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA |
| OAI Identifier: | oai:incliva.fundanetsuite.com:p4275 |
| Online Access: | https://incliva.portalinvestigacion.com/publicaciones/4275 |
| Access Level: | Open access |
| Keyword: | Ranolazine Human saphenous vein Coronary artery bypass grafting Vascular tone |
| Summary: | OBJECTIVES: Ranolazine improves vascular function in animal models. We evaluate the effects of ranolazine on vascular function and adrenergic response in human saphenous vein.; METHODS: Rings from 53 patients undergoing coronary artery bypass grafting were mounted in organ baths. Concentration-response curves to ranolazine were constructed in rings precontracted with phenylephrine, endothelin-1, vasopressin, KCl and the thromboxane A2 analogue U-46619. In rings precontracted with phenylephrine, relaxation to ranolazine was tested in the absence and presence of endothelial factors inhibitors, K+ channel blockers and verapamil. The effects of ranolazine on frequency-response and concentration-response curves to phenylephrine were performed in the absence and presence of endothelial factors inhibitors and K+ channel blockers. Endothelial nitric oxide synthase, alpha1 adrenergic receptor and large conductance Ca2+-activated K+ channel protein expressions were measured by Western blotting.; RESULTS: Ranolazine (10-9-10-4 M) produced a concentration-dependent relaxation only in rings precontracted with phenylephrine that was reduced by endothelial denudation, NG-nitro-l-arginine methyl ester (10-4 M), charybdotoxin (10-7 M) and verapamil (10-6 M). Ranolazine diminished adrenergic contractions induced by electrical field stimulation (2-4Hz) and phenylephrine (10-9-10-5 M) that were prevented by tetraethylammonium (10-3 M) and charybdotoxin (10-7 M). Ranolazine significantly decreased alpha1 adrenergic receptor and increased large conductance Ca2+-activated K+ channel protein expression in the saphenous vein.; CONCLUSIONS: Ranolazine diminishes the adrenergic vasoconstriction, acting as alpha1 antagonist, and by increasing large conductance Ca2+-activated K+ channel involvement. The relaxant effects of ranolazine are partially mediated by endothelial nitric oxide, large conductance Ca2+-activated K+ channels and the blockade of voltage-dependent Ca2+ channels. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. |
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