title: Chronic effects of endothelin-3 on blood pressure and renal haemodynamics in rats.
abstract: BACKGROUND
  Renal vasoconstriction and systemic hypertension are well-known effects of bolus or short-term endothelin administration. However, the role of endothelin as a circulating hormone remains largely unknown.
  
  
  METHODS
  The present study explores the effects of endothelin-3 (ET-3) on renal haemodynamics and systemic blood pressure during a 3-h and a 3-day intravenous infusion in rats. Male Sprague-Dawley (SD) rats were infused with vehicle (group 1) or ET-3 (group 2), 10 ng/kg per min; group 3, 50 ng/kg per min) delivered via osmotic minipumps into the right jugular vein for 3 days. On day 3 after pump implantation, rats were anaesthetized with Inactin and surgically prepared for assessment of mean arterial blood pressure (MABP), renal plasma flow (RPF), glomerular filtration rate (GFR), and renal vascular resistance (RVR). The same parameters were assessed during a 3-h ET-3 infusion study in SD rats (group 4, vehicle; group 5, ET-3, 10 ng/kg per min; group 6, ET-3, 50 ng/kg per min).
  
  
  RESULTS
  In 3-day infused rats, ET-3 induced a significant decrease in RPF (-22+/-7% and -26+/-8% for group 2 and group 3 respectively, P<0.05 vs group 1) and an increase in RVR (+40+/-11% for groups 2 and 3; P<0.05 vs group 1); 50 ng/kg per min ET-3 significantly decreased GFR (-17%, P<0.05 vs group 1). MABP was not significantly affected by endothelin infusion. In acute infusion studies a decrease of the same magnitude was seen for the renal haemodynamics values. 50 ng/kg per min ET-3 increased MABP; a systemic effect that disappeared after the 3-day infusion.
  
  
  CONCLUSIONS
  This study suggests that intravenously administered ET-3 in the rat has only a transient effect on systemic blood pressure, whereas it induces alterations in renal haemodynamics after both acute and chronic perfusions.
authors.affiliation: Services de Nephrologie et de Biochimie, Hôpital Pitie Salpêtrière, INSERM U 90, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Martinez
authors.forename: G
authors.initials: G
authors.lastname: Deray
authors.forename: M
authors.initials: M
authors.lastname: Dubois
authors.forename: C
authors.initials: C
authors.lastname: Jacquiaud
authors.forename: F
authors.initials: F
authors.lastname: Schmitt
authors.forename: C
authors.initials: C
authors.lastname: Jacobs
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016232:Endothelins