title: Cardiovascular effects of coumarins besides their antioxidant activity.
abstract: Coumarins are a large group of substances, primarily of plant origin. Like their more intensively examined congeners flavonoids, many of them are antioxidants. Although such properties may be advantageous in cardiovascular diseases, it has been shown that coumarins exhibit direct effects on the cardiovascular system which are not based on antioxidant activity. The most common example is the well-known drug warfarin, a synthetic compound derived from natural dicoumarol. Moreover, other coumarins have been shown to possess antiplatelet and vasodilatory potential. Interestingly, the former effect may be mediated by the inhibition of various pathways leading to platelet aggregation, their differing effects on those pathways being due to structural differences between the various coumarins. Conversely, their vasodilatory potential is linked in the majority of cases to the inhibition of increases in intracellular calcium concentration in vascular smooth muscle cells, and in several coumarins also to NO-mediated vasodilatation. Available data on both activities are summarized in this review. At the end of this review, relevant data are provided from a few studies testing the in vivo effects of coumarins on major cardiovascular diseases; the clinical use of warfarin and other coumarin anticoagulants, as well as the limited data on the clinical use of coumarins in chronic venous insufficiency and the possible toxicological effects of coumarins.
authors.forename: Iveta
authors.initials: I
authors.lastname: Najmanová
authors.forename: Martin
authors.initials: M
authors.lastname: Doseděl
authors.forename: Radomír
authors.initials: R
authors.lastname: Hrdina
authors.forename: Pavel
authors.initials: P
authors.lastname: Anzenbacher
authors.forename: Tomáš
authors.initials: T
authors.lastname: Filipský
authors.forename: Michal
authors.initials: M
authors.lastname: Říha
authors.affiliation: Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Department of Pharmacology and Toxicology, Heyrovskeho 1 203, 500 05 Hradec Kralove, Czech Republic. mladenkap@faf.cuni.cz.
authors.forename: Přemysl
authors.initials: P
authors.lastname: Mladěnka
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D002318:Cardiovascular Diseases / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002986:Clinical Trials as Topic; D003374:Coumarins / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D055808:Drug Discovery; D006801:Humans; D015394:Molecular Structure; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D014665:Vasodilator Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity
chemical_list: D000975:Antioxidants; D003374:Coumarins; D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents