The lignan eudesmin extracted from Piper truncatum induced vascular relaxation via activation of endothelial histamine H1 receptors.
In Brazilian folk medicine, extracts from Piper species are used to reduce blood pressure. Previously, we demonstrated the vasodilatory activity of crude extracts from leaves of Piper truncatum explaining their possible use in the treatment of hypertension in traditional medicine. In the present study, we investigated the effects of eudesmin, a lignan isolated from hexane extract of leaves from Piper truncatum, on the contractility of rat aortas and the possible mechanisms involved in its vascular action. Eudesmin induced an intense concentration-dependent relaxation of aortic rings precontracted with phenylephrine. The concentration of eudesmin necessary to reduce phenylephrine-induced aortic contraction by 50% (IC(50)) was 10.69+/-0.67 microg/ml. Eudesmin-induced vasodilation required an intact endothelium since vascular relaxation was inhibited by mechanic removal of endothelium, and by pretreatment with nitric oxide synthase inhibitor and soluble guanylate cyclase inhibitor. Relaxation induced by eudesmin was also impaired in the presence of indomethacin and diphenhydramine, a cyclooxygenase inhibitor and an antagonist of type 1 histamine receptor (H(1)), respectively. IC(50) was increased to 18.1+/-1.8 and 18.1+/-2.6 microg/ml (P<0.05; n=6) after exposure to indomethacin and diphenhydramine, respectively. Atropine (muscarinic receptor antagonist), propranolol (beta-adrenoceptor antagonist) and glibenclamide (ATP-sensitive K(+) channel blocker) did not alter the effect of eudesmin. These results indicate that eudesmin-induced vascular relaxation in rat aorta is mediated by release of nitric oxide and prostanoid through the involvement of histamine receptor present in the endothelial cells.
From Departamento de Farmacologia Básica e Clínica, ICB, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Juliana Montani
JM
Raimundo
Ana Paula Felix
AP
Trindade
Leosvaldo Salazar Marques
LS
Velozo
Maria Auxiliadora Coelho
MA
Kaplan
Roberto Takashi
RT
Sudo
Gisele
G
Zapata-Sudo
D000818:Animals; D001011:Aorta; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005663:Furans / Q000302:isolation & purification* / Q000494:pharmacology*; D006586:Hexanes / Q000737:chemistry; D066298:In Vitro Techniques; D017705:Lignans / Q000302:isolation & purification* / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D031701:Piper / Q000737:chemistry*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000302:isolation & purification / Q000494:pharmacology
D005663:Furans; D006586:Hexanes; D017705:Lignans; D010936:Plant Extracts; D011969:Receptors, Histamine H1; D014665:Vasodilator Agents; C105875:eudesmin