title: Involvement of bradykinin B2 and muscarinic receptors in the prolonged diuretic and antihypertensive properties of Echinodorus grandiflorus (Cham. & Schltdl.) Micheli.
abstract: BACKGROUND
  Although Echinodorus grandiflorus (Cham. & Schltr.) Michel are used in Brazilian folk medicine as a diuretic drug, to date, no study has evaluated the mechanisms involved in this activity after prolonged administration in rats.
  
  
  OBJECTIVE
  Evaluate the possible mechanisms involved in the prolonged diuretic activity of ethanol soluble fraction obtained from Echinodorus grandiflorus (ES-EG) and to assess its relationship with hypotensive and antihypertensive activity using normotensive rats and those with renovascular hypertension (2K1C).
  
  
  METHODS
  The diuretic effects of ES-EG (30-300 mg/kg; p.o.) were compared with hydrochlorothiazide in a repeated-dose treatment for 7 days. The urinary volume and sodium, potassium, chloride, bicarbonate contents, conductivity, pH and density were estimated in sample collected in 24 h for 7 days. Plasma sodium, potassium, total protein, urea, creatinine, aldosterone, vasopressin, nitrite, acetylcholinesterase concentration and angiotensin converting enzyme (ACE) activity were measured in samples collected at the end of the experimental period (seventh day). Using pharmacological antagonists or inhibitors, the involvement of bradykinin, prostaglandin, acetylcholine and nitric oxide (NO) in ES-EG-induced diuresis was determined. In addition, activities of erythrocytary carbonic anhydrase and renal Na+/K+/ATPase were evaluated in vitro.
  
  
  RESULTS
  ES-EG increased diuresis similarly to hydrochlorothiazide and also presented HCO3-sparing effects and increased serum nitrite levels. Moreover, the intraduodenal administration of ES-EG induces significant hypotensive and antihypertensive effects in 2K1C rats. Previous treatment with HOE-140, indometacin and atropine fully avoided the diuretic effect of ES-EG, and including L-NAME pre-administration, it prevented the hypotensive and hypertensive activity induced by ES-EG. In addition, the association between HOE-140 and atropine or indometacin and L-NAME fully inhibited the hypotensive and antihypertensive effects of ES-EG. The 7-day treatment with ES-EG resulted in increased plasma nitrite levels. All other parameters were not affected by treatment with ES-EG.
  
  
  CONCLUSIONS
  Our results suggest that the mechanisms through which Echinodorus grandiflorus extracts induce prolonged diuresis and reduce blood pressure in normotensive and 2K1C rats are mainly related to activation of muscarinic and bradykinin receptors with direct effects on prostaglandins and nitric oxide pathways.
authors.affiliation: Laboratório de Farmacologia e Toxicologia de Produtos Naturais, Universidade Paranaense, 4282 - Centro, Umuarama - PR, 87502-210, Brazil.
authors.forename: Thiago Buno Lima
authors.initials: TB
authors.lastname: Prando
authors.affiliation: Laboratório de Farmacologia e Toxicologia de Produtos Naturais, Universidade Paranaense, 4282 - Centro, Umuarama - PR, 87502-210, Brazil.
authors.forename: Lorena Neris
authors.initials: LN
authors.lastname: Barboza
authors.affiliation: Laboratório de Farmacologia e Toxicologia de Produtos Naturais, Universidade Paranaense, 4282 - Centro, Umuarama - PR, 87502-210, Brazil.
authors.forename: Valdinei de Oliveira
authors.initials: Vde O
authors.lastname: Araújo
authors.affiliation: Laboratório de Farmacologia Cardiovascular, Faculdade de Ciências da Saúde, Universidade Federal da Grande Dourados, Rodovia Dourados-Itahum, km 12, P.O. Box 533, 79.804-970, Dourados, MS, Brazil.
authors.forename: Francielly Mourão
authors.initials: FM
authors.lastname: Gasparotto
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, P.O. Box 19046, 81.531-980, Curitiba, PR, Brazil. Electronic address: laurosouza@hotmail.com.
authors.forename: Lauro Mera
authors.initials: LM
authors.lastname: de Souza
authors.affiliation: Laboratório de Farmacologia e Toxicologia de Produtos Naturais, Universidade Paranaense, 4282 - Centro, Umuarama - PR, 87502-210, Brazil.
authors.forename: Emerson Luiz Botelho
authors.initials: EL
authors.lastname: Lourenço
authors.affiliation: Laboratório de Farmacologia Cardiovascular, Faculdade de Ciências da Saúde, Universidade Federal da Grande Dourados, Rodovia Dourados-Itahum, km 12, P.O. Box 533, 79.804-970, Dourados, MS, Brazil . Electronic address: arquimedesgasparotto@gmail.com.
authors.forename: Arquimedes
authors.initials: A
authors.lastname: Gasparotto Junior
mesh_terms: D034901:Alismataceae / Q000737:chemistry; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001938:Brazil; D004232:Diuretics / Q000494:pharmacology* / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008519:Medicine, Traditional; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D004232:Diuretics; D018727:Muscarinic Antagonists; D010936:Plant Extracts; D001920:Bradykinin
keywords: Antihypertensive; Bradykinin; Diuretic; Echinodorus grandiflorus; Nitric oxide; Prostaglandins