title: Hypotensive effect of Aspidosperma subincanum Mart. in rats and its mechanism of vasorelaxation in isolated arteries.
abstract: BACKGROUND
  Aspidosperma subincanum is a medicinal herb that is known to be useful for the treatment of cardiovascular-related illnesses. However, its effects and pharmacological mechanisms of action have not been studied. The aim of the present study was to determine the effect of an ethanol extract of Aspidosperma subincanum (EEAS) on blood pressure (in vivo) and vascular tension (in vitro) in the rat thoracic aorta.
  
  
  METHODS
  Catheters were inserted into the right femoral vein and artery of anesthetized rats for EEAS infusion and the measurement of blood pressure, heart rate and aortic blood flow (flow probes were placed around the aorta). Moreover, the vasodilator effect of EEAS in isolated pre-contracted rat aortas was examined.
  
  
  RESULTS
  Intravenous infusion of EEAS resulted in significant and dose-dependent hypotension, bradycardia and increased aortic blood flow. In isolated arteries, EEAS (0-27 μg/mL) induced a concentration-dependent relaxation of pre-contracted aortic rings; endothelial denudation potentiated this effect. Pre-treatment of the aortic rings with ODQ, an inhibitor of soluble guanylyl cyclase (sGC); MDL-12,330A, an inhibitor of adenylyl cyclase (AC); or CPA, a SERCA inhibitor, reduced EEAS-induced vasorelaxation. Treatment with an EEAS impaired contractions induced by phenylephrine (an adrenergic agonist) and Bay K 8644 (an L-type Ca(2+) channel activator). The blockade of K(+) channels with tetraethylammonium, clotrimazole, glibenclamide or 4-aminopyridine reduced the relaxation stimulated by EEAS.
  
  
  CONCLUSIONS
  These findings suggest that EEAS induces hypotension associated with bradycardia. EEAS induces endothelium-independent vascular relaxation. The sGC/cGMP and AC/cAMP pathways, SERCA activation and Ca(2+) and K(+) flux across the sarcolemma, are likely involved in this relaxation.
authors.affiliation: Faculty of Pharmacy, Federal University of Goias, Avenida Universitária s/n, 74605-220 Goiânia, GO, Brazil.
authors.forename: Milton Junio Cândido
authors.initials: MJ
authors.lastname: Bernardes
authors.forename: Flávio Silva
authors.initials: FS
authors.lastname: de Carvalho
authors.forename: Ludmila
authors.initials: L
authors.lastname: Lima Silveira
authors.forename: José Realino
authors.initials: JR
authors.lastname: de Paula
authors.forename: Maria Teresa Freitas
authors.initials: MT
authors.lastname: Bara
authors.forename: Clévia Ferreira
authors.initials: CF
authors.lastname: Garrote
authors.forename: Gustavo Rodrigues
authors.initials: GR
authors.lastname: Pedrino
authors.forename: Matheus Lavorenti
authors.initials: ML
authors.lastname: Rocha
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000322:Adrenergic Agonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D030009:Aspidosperma / Q000737:chemistry; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D000431:Ethanol / Q000737:chemistry; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D041743:Herb-Drug Interactions / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D010656:Phenylephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010936:Plant Extracts / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000322:Adrenergic Agonists; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D026902:Potassium Channel Blockers; D014665:Vasodilator Agents; D010656:Phenylephrine; D000431:Ethanol; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester