title: Cardiovascular effects of a labdenic diterpene isolated from Moldenhawera nutans in conscious, spontaneously hypertensive rats.
abstract: BACKGROUND
  The labdenic diterpene labd-8(17)-en-15-oic acid (labd-8) isolated from a methanolic extract of Moldenhawera nutans Queiroz & Alkin (Leguminosae) has hypotensive and tachycardiac properties in normotensive rats. A part of the hypotensive effect was due to a reduction in the sympathetic nerve drive to vessels, an event admittedly enhanced in spontaneously hypertensive rats (SHRs).
  
  
  OBJECTIVE
  We assessed whether the cardiovascular effects induced by labd-8 could be enhanced in SHRs.
  
  
  METHODS
  For in vivo experiments, arterial and venous catheters were implanted under anesthesia for blood pressure recording and drug administration, respectively. For in vitro experiments, thoracic aorta rings were suspended in organ baths containing warm (37 °C) perfusion medium that was continuously bubbled with carbogen.
  
  
  RESULTS
  Intravenous injection of labd-8 (1, 3, 5, and 10 mg/kg) induced similar dose-dependent hypotension and tachycardia in both SHRs and Wistar-Kyoto rats (WKY). In SHRs, only the tachycardia response to labd-8 was significantly reduced by pretreatment with methylatropine or propranolol. However, both cardiovascular effects of labd-8 were reduced by hexamethonium while remained unchanged by l-NAME. In isolated aortic preparations from SHRs, labd-8 (1-1000 µg/mL) relaxed potassium-induced contractions with an IC50 (geometric mean [95% confidence interval]) value (536.5 [441.0-631.9] µg/mL) significantly greater than that (157.6 [99.1-250.5] µg/mL) obtained in preparations from WKY rats.
  
  
  CONCLUSIONS
  In SHRs, the hypotension induced by labd-8 is associated with a reflex tachycardia and seems mediated partly through withdrawal of sympathetic vasomotor tone and partly through an active vasorelaxation. Its magnitude was not enhanced when compared with WKY rats likely because of impaired vasorelaxant effects of labd-8 in preparations from SHRs.
authors.affiliation: Department of Physiology and Pharmacology, Federal University of Pernambuco , Recife, PE , Brazil .
authors.forename: Carlos Antônio
authors.initials: CA
authors.lastname: de Barros Correia Junior
authors.forename: Rodrigo José
authors.initials: RJ
authors.lastname: Bezerra de Siqueira
authors.forename: Leylliane Fátima
authors.initials: LF
authors.lastname: Leal Interaminense
authors.forename: Thayane Rebeca
authors.initials: TR
authors.lastname: Alves-Santos
authors.forename: Gloria Pinto
authors.initials: GP
authors.lastname: Duarte
authors.forename: Jorge Maurício
authors.initials: JM
authors.lastname: David
authors.forename: Juceni Pereira
authors.initials: JP
authors.lastname: David
authors.forename: Pedro Jorge Caldas
authors.initials: PJ
authors.lastname: Magalhães
authors.forename: Saad
authors.initials: S
authors.lastname: Lahlou
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001341:Autonomic Nervous System / Q000187:drug effects; D004224:Diterpenes / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use*; D007887:Fabaceae / Q000737:chemistry*; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D010936:Plant Extracts / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use*; D018547:Plant Stems / Q000737:chemistry; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity; D013610:Tachycardia / Q000139:chemically induced* / Q000209:etiology
chemical_list: D000959:Antihypertensive Agents; D004224:Diterpenes; D010936:Plant Extracts; C518472:labd-8 (17)-en-15-oic acid
keywords: Autonomic nervous system; hypotension; isolated rat aorta; labd-8(17)-en-15-oic acid; relaxation; tachycardia