Pharmacological mechanisms involved in the vasodilator effects of extracts from Echinodorus grandiflorus.
We investigated the vascular effects of a crude aqueous extract (AEEG) of Echinodorus grandiflorus (Alismataceae) using the in vitro experimental models of the rabbit isolated aorta and perfused kidney. Echinodorus grandiflorus, a native semi-aquatic plant widely distributed in Brazil, has been extensively used in Brazilian folk medicine for the treatment of high blood pressure and inflammatory diseases. The bolus injection of AEEG (0.1-10 mg) into the rabbit renal circulation pre-contracted with norepinephrine induced marked and dose-dependent vasodilator responses (maximum of 37+/-4%; n=6; P<0.001), which was similar to that induced by injection of 10 mmol acetylcholine (41+/-3%). Moreover, AEEG elicited a significant and concentration-dependent relaxation in the endothelium-intact, but not endothelium-denuded aortic rings, reaching the maximum of 81+/-5% (n=7, P<0.001). Inhibition of the nitric oxide-cGMP pathway with L-NAME (100 microM) or Methylene Blue (20 microM) reduced maximum relaxation induced by AEEG from 81+/-5% to 46+/-3 and 45+/-3%, respectively (n=7, P<0.001). A similar reduction was obtained with the incubation of the aortic rings with the selective PAF receptor antagonist WEB 2086 (10 microM) (from 81+/-5% to 55+/-3%; n=7; P<0.01). Conversely, blockade of muscarinic receptors with atropine (10 microM) did not affect the vasodilator effects of AEEG, while inhibition of the enzyme cyclooxigenase not only did not block, but rather potentiated vasodilation induced by AEEG (n=7, P<0.001). Finally, blockade of Ca(2+)- and ATP-activated K(+) channels using the specific blockers charydbotoxin (100 nM) and glibenclamide (3 microM), respectively, did not modify aortic relaxation induced by AEEG. We conclude that water-soluble extracts from leaves of Echinodorus grandiflorus elicit an endothelium-dependent, nitric oxide and PAF receptor-mediated vasodilation in rabbit aortic rings, which does not appear to involve the generation of vasodilating prostaglandins or the activation of K(+) channels. This potent vasodilator effect of the extracts was confirmed in the isolated rabbit renal circulation.
Tibiriçá
Eduardo
E
Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil. etibi@ioc.fiocruz.br
Almeida
Andressa
A
Caillleaux
Solange
S
Pimenta
Daniel
D
Kaplan
Maria Auxiliadora
MA
Lessa
Marcos Adriano
MA
Figueiredo
Maria Raquel
MR
D034901:Alismataceae; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D001381:Azepines / Q000494:pharmacology; D001938:Brazil; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism; D008751:Methylene Blue / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D018515:Plant Leaves; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects*; D014230:Triazoles / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D001381:Azepines; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; D014665:Vasodilator Agents; C039351:platelet activating factor receptor; C052518:WEB 2086; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester