title: Antihypertensive effects of isoquercitrin and extracts from Tropaeolum majus L.: evidence for the inhibition of angiotensin converting enzyme.
abstract: OBJECTIVE
  Previous studies have shown that the extracts obtained from Tropaeolum majus L. exhibit pronounced diuretic properties. In the present study, we assessed whether the hypotensive and/or antihypertensive mechanism of hydroethanolic extract (HETM), semi-purified fraction (TMLR) obtained from T. majus and the flavonoids isoquercitrin (ISQ) and kaempferol (KPF) can be mediated by their interaction with angiotensin converting enzyme (ACE).
  
  
  METHODS
  Firstly, to evaluate changes in mean arterial pressure (MAP), different groups of normotensive and spontaneously hypertensive rats (SHR) were orally and intraduodenally treated with HETM (10-300 mg/kg) and TMLR (12.5-100mg/kg) and intravenously treated with ISQ and KPF being later anesthetized with ketamine (100mg/kg) and xylazine (20mg/kg). The left femoral vein and the right carotid artery were isolated, and polyethylene catheters were inserted for ISQ and KPF (0.5-4 mg/kg) administration and blood pressure recording, respectively. The plasmatic ACE activity was evaluated to indirect fluorimetry, in serum samples after orally treatment with HETM, TMLR, ISQ and KPF.
  
  
  RESULTS
  The oral administration of the HETM and its TMLR significantly reduced, in a dose-dependent manner, the MAP in both normotensive and SHR. In addition, these preparations significantly decreased the MAP for up to 3h after the administration of the extract. Additionally, the intravenous administration of ISQ, but not KPF, decreased MAP in rats. Otherwise, neither the extracts nor ISQ affected the heart rate. The oral administration of the HETM, TMLR or ISQ reduced ACE activity in serum samples at 90 min after administration. Finally, the intravenous administration of ISQ caused a significant reduction in the hypertensive response to angiotensin I, but not angiotensin II in normotensive rats.
  
  
  CONCLUSIONS
  Our results show that the hypotensive effects caused by the HETM, as well as by its TMLR, may be associated with the high levels of the flavonoid ISQ found in this plant. In addition, ISQ-induced hypotension in rats is an event dependent on the inhibition of angiotensin II generation by ACE.
authors.affiliation: Department of Pharmacology, Universidade Paranaense, Umuarama, PR, Brazil. gasparotto@unipar.br
authors.forename: Arquimedes
authors.initials: A
authors.lastname: Gasparotto Junior
authors.forename: Francielly Mourão
authors.initials: FM
authors.lastname: Gasparotto
authors.forename: Emerson Luiz Botelho
authors.initials: EL
authors.lastname: Lourenço
authors.forename: Sandra
authors.initials: S
authors.lastname: Crestani
authors.forename: Maria Elida Alves
authors.initials: ME
authors.lastname: Stefanello
authors.forename: Marcos José
authors.initials: MJ
authors.lastname: Salvador
authors.forename: José Eduardo
authors.initials: JE
authors.lastname: da Silva-Santos
authors.forename: Maria Consuelo Andrade
authors.initials: MC
authors.lastname: Marques
authors.forename: Cândida Aparecida Leite
authors.initials: CA
authors.lastname: Kassuya
mesh_terms: D000803:Angiotensin I / Q000037:antagonists & inhibitors; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000032:analysis / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000032:analysis / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D018515:Plant Leaves; D011794:Quercetin / Q000031:analogs & derivatives* / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D032388:Tropaeolum / Q000737:chemistry*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D010936:Plant Extracts; C016527:isoquercitrin; D000803:Angiotensin I; D011794:Quercetin; D007703:Peptidyl-Dipeptidase A