title: Mechanisms underlying the diuretic effects of Tropaeolum majus L. extracts and its main component isoquercitrin.
abstract: BACKGROUND
  Previous studies have shown that the extracts obtained from Tropaeolum majus L., and its main compound isoquercitrin (ISQ), exhibit pronounced diuretic effects, supporting the ethnopharmacological use of this plant. The aim of this study was to evaluate the efficacy and mechanisms underlying the diuretic action of an ethanolic extract of Tropaeolum majus (HETM), its purified fraction (TMLR), and its main compound ISQ, in spontaneously hypertensive rats (SHR).
  
  
  METHODS
  The diuretic effects of HETM (300mg/kg; p.o.), TMLR (100mg/kg; p.o.), and ISQ (10mg/kg; p.o.), were compared with classical diuretics in 7days repeated-dose treatment. The urinary volume, sodium, potassium, chloride, bicarbonate, conductivity, pH and density were estimated in the sample collected for 15h. The plasmatic concentration of sodium, potassium, urea, creatinine, aldosterone, vasopressin, nitrite and angiotensin converting enzyme (ACE) activity were measured in samples collected at the end of the experiment (seventh day). Using pharmacological antagonists or inhibitors, we determine the involvement of bradykinin, prostaglandin and nitric oxide (NO) in ISQ-induced diuresis. In addition, reactive oxygen species (ROS) and the activity of erythrocytary carbonic anhydrase and renal Na(+)/K(+)/ATPase were evaluated in vitro.
  
  
  RESULTS
  HETM, TMLR and ISQ increased diuresis similarly to spironolactone and also presented K(+)-sparing effects. All groups presented both plasmatic aldosterone levels and ACE activity reduced. Previous treatment with HOE-140 (a B2-bradykinin receptor antagonist), or indomethacin (a cyclooxygenase inhibitor), or L-NAME (a NO synthase inhibitor), fully avoided the diuretic effect of ISQ. In addition, the 7days treatment with ISQ resulted in increased plasmatic levels of nitrite and reducing ROS production. Moreover, the renal Na(+)/K(+)/ATPase activity was significantly decreased by ISQ.
  
  
  CONCLUSIONS
  Our results suggest that the mechanisms through ISQ and extracts of Tropaeolum majus increase diuresis in SHR rats are mainly related to ACE inhibition, increased bioavailability of bradykinin, PGI2, and nitric oxide, besides an inhibitory effect on Na(+)/K(+)-ATPase.
authors.affiliation: Institute of Biological Sciences, Medical and Health, Universidade Paranaense, Umuarama, PR, Brazil. gasparotto@unipar.br
authors.forename: Arquimedes
authors.initials: A
authors.lastname: Gasparotto Junior
authors.forename: Thiago Bruno Lima
authors.initials: TB
authors.lastname: Prando
authors.forename: Thiago Dos Santos Vilhena
authors.initials: Tdos S
authors.lastname: Leme
authors.forename: Francielly Mourão
authors.initials: FM
authors.lastname: Gasparotto
authors.forename: Emerson Luiz Botelho
authors.initials: EL
authors.lastname: Lourenço
authors.forename: Yanna Dantas
authors.initials: YD
authors.lastname: Rattmann
authors.forename: José Eduardo
authors.initials: JE
authors.lastname: Da Silva-Santos
authors.forename: Cândida Aparecida Leite
authors.initials: CA
authors.lastname: Kassuya
authors.forename: Maria Consuelo Andrade
authors.initials: MC
authors.lastname: Marques
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001920:Bradykinin / Q000378:metabolism; D004195:Disease Models, Animal; D004231:Diuresis / Q000187:drug effects*; D004232:Diuretics / Q000302:isolation & purification / Q000494:pharmacology*; D011464:Epoprostenol / Q000378:metabolism; D000431:Ethanol / Q000737:chemistry; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves; D010946:Plants, Medicinal; D011794:Quercetin / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D015398:Signal Transduction / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism; D012997:Solvents / Q000737:chemistry; D013997:Time Factors; D032388:Tropaeolum / Q000737:chemistry
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D004232:Diuretics; D010936:Plant Extracts; D012997:Solvents; C016527:isoquercitrin; D009569:Nitric Oxide; D000431:Ethanol; D011794:Quercetin; D011464:Epoprostenol; D000254:Sodium-Potassium-Exchanging ATPase; D001920:Bradykinin