Actions of calcium channel blockers on vascular proteoglycan synthesis: relationship to atherosclerosis.
Calcium channel blockers (CCBs) are a widely used group of antihypertensive agents. CCBs are efficacious in the reduction of blood pressure but the extent to which they manifest beneficial effects on cardiovascular disease is variable. Clinical studies indicate that pleiotropic actions make significant contributions to the efficacy of agents aimed at preventing atherosclerosis. The "response to retention" hypothesis implicates the binding and retention of lipoproteins by glycosaminoglycan chains on proteoglycans as an initiating step in atherogenesis. Atherogenic factors act as agonists and several classes of drugs including peroxisome proliferating-activated receptor (PPAR)-alpha and -gamma ligands act as antagonists in this model. Initial data have demonstrated that high concentrations of CCBs inhibit proteoglycan synthesis. Newer preliminary data show that the action is very modest at reasonable concentrations and appears to be independent of calcium channel blocking activity. We have reviewed the role of cardiovascular drugs acting on vascular smooth muscle proteoglycan synthesis and considered the potential action of CCBs in this model. We conclude that the inhibition of proteoglycan synthesis by CCBs does not play a role in the attenuation of atherosclerosis; however, the antihypertensive efficacy and alternative beneficial actions provide support for the use of CCBs in the therapy of cardiovascular disease.
Survase
Soniya
S
Cell Biology of Diabetes Laboratory, Baker Heart Research Institute, Melbourne, VIC, Australia.
Ivey
Melanie E
ME
Nigro
Julie
J
Osman
Narin
N
Little
Peter J
PJ
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D050356:Lipid Metabolism / Q000187:drug effects; D008074:Lipoproteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D011509:Proteoglycans / Q000096:biosynthesis*
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D008074:Lipoproteins; D011509:Proteoglycans; D002118:Calcium