title: Activation of muscarinic receptors by a hydroalcoholic extract of Dicksonia sellowiana Presl. HooK (Dicksoniaceae) induces vascular relaxation and hypotension in rats.
abstract: Dicksonia sellowiana (Presl.) Hook is a native plant from the Central and South Americas that contain high levels of polyphenols, antioxidant compounds involved in protection against inflammation, cancer and cardiovascular risk. A phytomedicinal preparation obtained from aerial parts of D. sellowiana is currently under clinical evaluation in Brazil against asthma, and has been associated with several other beneficial effects. This study demonstrates that a hydroalcoholic extract obtained from D. sellowiana leaves (HEDS) fully relax, in a concentration-dependent manner, rat aortic rings precontracted with phenylephrine. Moreover, administration of HEDS (10, 20 and 40 mg/kg, i.v.) in anaesthetized rats resulted in a strong but reversible hypotension. Aortic relaxation induced by HEDS was abolished by endothelium removal, by incubation of the nitric oxide synthase inhibitor L-NAME, or the soluble guanylate cyclase inhibitor ODQ. In addition, this effect was partially inhibited by indomethacin (a cyclooxygenase inhibitor) and KT 5730 (a PKA inhibitor). The potassium channels blockade by either tetraethylammonium or charybdotoxin also resulted in a potent inhibition of HEDS-induced aortic relaxation, whereas apamine only slightly reduced it. In addition HEDS-induced relaxation was unchanged by 4-amynopiridine and glibenclamide. The selective muscarinic receptor antagonist atropine counteracted both aortic relaxation and blood pressure reduction generated by HEDS. Experiments using HPLC revealed the presence of high amounts of phenolic compounds in this extract. Taken together, our results reveal that the D. sellowiana possess substances with both in vivo and in vitro activities and that the vascular effect of HEDS involves activation of muscarinic receptors, stimulation of the nitric oxide pathway and opening of calcium-activated potassium channels.
authors.affiliation: Department of Pharmacology, Centro Politécnico, Universidade Federal do Paraná, Curitiba, PR, Brazil.
authors.forename: Yanna D
authors.initials: YD
authors.lastname: Rattmann
authors.forename: Sandra
authors.initials: S
authors.lastname: Crestani
authors.forename: Fernanda R
authors.initials: FR
authors.lastname: Lapa
authors.forename: Obdúlio G
authors.initials: OG
authors.lastname: Miguel
authors.forename: Maria C A
authors.initials: MC
authors.lastname: Marques
authors.forename: J Eduardo
authors.initials: JE
authors.lastname: da Silva-Santos
authors.forename: Adair R S
authors.initials: AR
authors.lastname: Santos
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D029624:Ferns; D007022:Hypotension / Q000209:etiology / Q000503:physiopathology; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D018721:Muscarinic Agonists; D010936:Plant Extracts; D024681:Potassium Channels, Calcium-Activated; D011976:Receptors, Muscarinic; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester