Novel Vascular Biology of Third-Generation L-Type Calcium Channel Antagonists
Open Access
- 1 December 2003
- journal article
- review article
- Published by Wolters Kluwer Health in Arteriosclerosis, Thrombosis, and Vascular Biology
- Vol. 23 (12), 2155-2163
- https://doi.org/10.1161/01.atv.0000097770.66965.2a
Abstract
Calcium channel blockers (CCBs) were developed as vasodilators, and their use in cardiovascular disease treatment remains largely based on that mechanism of action. More recently, with the evolution of second- and third-generation CCBs, pleiotropic effects have been observed, and at least some of CCBs’ benefit is attributable to these mechanisms. Understanding these effects has contributed greatly to elucidating disease mechanisms and the rationale for CCB use. Furthermore, this knowledge might clarify why drugs are useful in some disease states, such as atherosclerosis, but not in others, such as heart failure. Although numerous drugs used in the treatment of vascular disease, including statins and angiotensin-converting–enzyme inhibitors, have well-described pleiotropic effects universally accepted to contribute to their benefit, little attention has been paid to CCBs’ potentially similar effects. Accumulating evidence that at least 1 CCB, amlodipine, has pharmacologic actions distinct from L-type calcium channel blockade prompted us to investigate the pleiotropic actions of amlodipine and CCBs in general. There are several areas of research; foci here are (1) the physicochemical properties of amlodipine and its interaction with cholesterol and oxidants; (2) the mechanism by which amlodipine regulates NO production and implications; and (3) amlodipine’s role in controlling smooth muscle cell proliferation and matrix formation.Keywords
This publication has 81 references indexed in Scilit:
- Major Outcomes in High-Risk Hypertensive Patients Randomized to Angiotensin-Converting Enzyme Inhibitor or Calcium Channel Blocker vs Diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)JAMA, 2002
- Amlodipine, but not verapamil or nifedipine, dilates rabbit femoral artery largely through a nitric oxide‐ and kinin‐dependent mechanismBritish Journal of Pharmacology, 2002
- Reduced coronary vasodilator responses to amlodipine in pacing-induced heart failure in conscious dogs: role of nitric oxideBritish Journal of Pharmacology, 2002
- Membrane Antioxidant Effects of the Charged Dihydropyridine Calcium Antagonist AmlodipineJournal of Molecular and Cellular Cardiology, 1999
- Oxidized low-density lipoprotein increases the production of intracellular reactive oxygen species in endothelial cellsJournal Of Hypertension, 1998
- In Vitro Antioxidant Activity of Calcium Antagonists against LDL Oxidation Compared with α-TocopherolBiochemical and Biophysical Research Communications, 1994
- Pharmacology of smooth muscle cell replication.Hypertension, 1992
- Antioxidant properties of active and inactive isomers of nicardipine in cardiac membranes, endothelial cells, and perfused rat heartsCoronary Artery Disease, 1992
- Pharmacologic profile of amlodipineThe American Journal of Cardiology, 1989
- Cholesterol and the cell membraneBiochimica et Biophysica Acta (BBA) - Reviews on Biomembranes, 1985