Vascular protective effects of dihydropyridine calcium antagonists. Involvement of endothelial nitric oxide.
Dihydropyridine calcium antagonists play an important role in the treatment of hypertension and angina pectoris. They lower blood pressure by a well-characterized mechanism of blocking L-type calcium channels in smooth muscle cells. Additionally, there is growing evidence that dihydropyridines also modulate endothelial functions by other mechanisms, since macrovascular endothelial cells do not express L-type calcium channels. A number of studies have demonstrated that dihydropyridine calcium antagonists enhance bioavailability of endothelial nitric oxide (NO). Endothelium-derived NO plays a pivotal role in the regulation of vasorelaxation, leukocyte adhesion and platelet aggregation and an impaired NO release is associated with the genesis and progression of atherosclerotic diseases. This review summarizes results from experimental findings that dihydropyridine calcium antagonists increase endothelial NO formation as well as studies which demonstrate these effects in vivo both in animals and humans. Moreover, the influence of dihydropyridine calcium antagonists on the progression of atherosclerosis is discussed. These pleiotropic effects of dihydropyridine calcium antagonists may underlie or contribute to antiatherosclerotic effects of this substance class.
Berkels
Reinhard
R
Institut für Pharmakologie, Klinikum der Universität zu Köln, Köln, Deutschland. Reinhard.Berkels@medizin.uni-keoln.de
Taubert
Dirk
D
Rosenkranz
Anke
A
Rösen
Renate
R
D000818:Animals; D001161:Arteriosclerosis / Q000517:prevention & control; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D004095:Dihydropyridines / Q000494:pharmacology* / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase