Effects of anethole and structural analogues on the contractility of rat isolated aorta: Involvement of voltage-dependent Ca2+-channels.
Anethole is a naturally occurring aromatic oxidant, present in a variety of medicinal plant extracts, which is commonly used by the food and beverage industry. Despite its widespread occurrence and commercial use, there is currently little information regarding effects of this compound on the vasculature. Therefore the actions of anethole on the contractility of rat isolated aorta were compared with those of eugenol, and their respective isomeric forms, estragole and isoeugenol. In aortic rings precontracted with phenylephrine (PE; 1 microM), anethole (10(-6) M-10(-4) M) induced contraction in preparations possessing an intact endothelium, but not in endothelium-denuded tissues. At higher concentrations (10(-3) M-10(-2) M), anethole-induced concentration-dependent and complete relaxation of all precontracted preparations, irrespective of whether the endothelium was intact or not, an action shared by eugenol, estragole and isoeugenol. The contractile and relaxant effects of anethole in PE-precontracted preparations were not altered by L-NAME (10 microM) or indomethacin (10 microM), indicating that neither nitric oxide nor prostaglandins were involved in these actions. The mixed profile of effects was not confined to PE-mediated contraction, since similar responses were obtained to anethole when tissues were precontracted with 25 mM KCl. Anethole and estragole (10(-6)-10(-4) M), but not eugenol or isoeugenol, increased the basal tonus of endothelium-denuded aortic rings, an action that was abolished by VDCC blockers nifedipine (1 microM) and diltiazem (1 microM), or by withdrawal of extracellular Ca(2+). Our data suggest complex effects of anethole on isolated blood vessels, inducing contraction at lower doses, mediated via opening of voltage-dependent Ca(2+)-channels, and relaxant effects at higher concentrations that are shared by structural analogues.
Soares
Pedro Marcos G
PM
Instituto Superior de Ciências Biomédicas, ISCB-CCS, Universidade Estadual do Ceará, Av. Paranjana 1700, 60740-000, Fortaleza-CE, Brazil.
Lima
Ricardo F
RF
de Freitas Pires
Alana
A
Souza
Emmanuel P
EP
Assreuy
Ana Maria S
AM
Criddle
David N
DN
D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D001011:Aorta / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D002317:Cardiovascular Agents / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005421:Flavoring Agents / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D009924:Organ Culture Techniques; D016877:Oxidants / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D000081248:Allylbenzene Derivatives; D000840:Anisoles; D015220:Calcium Channels; D002317:Cardiovascular Agents; D004791:Enzyme Inhibitors; D005421:Flavoring Agents; D016877:Oxidants; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D004110:Diltiazem; D009543:Nifedipine; C006578:anethole; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin