Effect of an alpha-blocker (Nicergoline) and of a beta-blocker (Acebutolol) on the in vitro biosynthesis of vascular extracellular matrix.
The effect of an alpha-blocking agent and of a beta-blocking agent on the biosynthesis of extracellular matrix macromolecules of the arterial wall was investigated. Rabbit aorta explants were cultured up to 48 hours with radioactive proline, lysine or glucosamine. In presence of these drugs, at concentration shown to be effective for the inhibition of platelet-endothelial cell interactions (10(-7) M), the incorporation of 14C proline in total macromolecular proline was higher than in macromolecular hydroxyproline suggesting a relatively higher rate of biosynthesis of non-collagenous proteins as compared to collagens. The alpha-blocking increased the incorporation of 14C proline in collagenous and non-collagenous proteins after 18 hours of incubation. beta-blocking also increased the incorporation of proline in macromolecular proline and hydroxyproline as compared to control cultures. Both increased the incorporation of 3H glucosamine in newly synthesised glycosaminoglycans. beta-blocking increased mainly the neosynthesis of heparan sulphate, alpha-blocking that of hyaluronan. The incorporation of 14C-lysine in crosslinked, insoluble elastin was not modified. These experiments confirm that alpha and beta-blocking agents can influence not only the tonus of aortic smooth muscle cells but also the relative rates of biosynthesis of extracellular matrix macromolecules. This effect should be taken in consideration for the evaluation of the long range effect of alpha and beta-blocking drugs on the vascular wall.
Moczar
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Laboratoire de recherche chirurgicale, hôpital Henri Mondor, 51, avenue du Maréchal de Lattre de Tassigny, 94000 Créteil, France.
Robert
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AM
Jacotot
B
B
Robert
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D000070:Acebutolol / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta; D001158:Arteries / Q000187:drug effects / Q000648:ultrastructure*; D002250:Carbon Radioisotopes; D003094:Collagen / Q000096:biosynthesis; D046508:Culture Techniques; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D005944:Glucosamine / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis; D006497:Heparan Sulfate / Q000096:biosynthesis; D006820:Hyaluronic Acid / Q000096:biosynthesis; D006909:Hydroxyproline / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009530:Nicergoline / Q000494:pharmacology*; D011392:Proline / Q000378:metabolism; D011817:Rabbits; D014316:Tritium
D000070:Acebutolol; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002250:Carbon Radioisotopes; D003094:Collagen; D016326:Extracellular Matrix Proteins; D005944:Glucosamine; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D006820:Hyaluronic Acid; D006909:Hydroxyproline; D008239:Lysine; D009530:Nicergoline; D011392:Proline; D014316:Tritium