title: Blockade of tachykinin NK3 receptor reverses hypertension through a dopaminergic mechanism in the ventral tegmental area of spontaneously hypertensive rats.
abstract: OBJECTIVE
  Intracerebroventricularly injected tachykinin NK(3) receptor (R) antagonists normalize mean arterial blood pressure (MAP) in spontaneously hypertensive rats (SHR). This study was pursued to define the role played by NK(3)R located on dopamine neurones of the ventral tegmental area (VTA) in the regulation of MAP in SHR.
  
  
  METHODS
  SHR (16 weeks) were implanted permanently with i.c.v. and/or VTA guide cannulae. Experiments were conducted 24 h after catheterization of the abdominal aorta to measure MAP and heart rate (HR) in freely behaving rats. Cardiovascular responses to i.c.v. or VTA-injected NK(3)R agonist (senktide) and antagonists (SB222200 and R-820) were measured before and after systemic administration of selective antagonists for D(1)R (SCH23390), D(2)R (raclopride) or non-selective D(2)R (haloperidol), and after destruction of the VTA with ibotenic acid.
  
  
  RESULTS
  I.c.v. or VTA-injected SB222200 and R-820 (500 pmol) evoked anti-hypertension, which was blocked by raclopride. Senktide (10, 25, 65 and 100 pmol) elicited greater increases of MAP and HR when injected in the VTA, and the cardiovascular response was blocked by R-820, SCH23390 and haloperidol. VTA-injected SB222200 prevented the pressor response to i.c.v. senktide, and vice versa, i.c.v. senktide prevented the anti-hypertension to VTA SB222200. Destruction of the VTA prevented the pressor response to i.c.v. senktide and the anti-hypertension to i.c.v. R-820.
  
  
  CONCLUSIONS
  The NK(3)R in the VTA is implicated in the maintenance of hypertension by increasing midbrain dopaminergic transmission in SHR. Hence, this receptor may represent a therapeutic target in the treatment of hypertension.
authors.affiliation: Département de Physiologie, Faculté de médecine, Université de Montréal, Montréal, Quebec, Canada.
authors.forename: Helaine
authors.initials: H
authors.lastname: De Brito Gariepy
authors.forename: Réjean
authors.initials: R
authors.lastname: Couture
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D006220:Haloperidol / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D007051:Ibotenic Acid / Q000494:pharmacology; D007211:Indoles / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009842:Oligopeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000494:pharmacology; D011804:Quinolines / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D018042:Receptors, Neurokinin-3 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology*
chemical_list: D001552:Benzazepines; D007211:Indoles; D009842:Oligopeptides; D010446:Peptide Fragments; D011804:Quinolines; C109443:R 820; D018042:Receptors, Neurokinin-3; C109112:SB 222200; C534628:SCH 23390; C054724:senktide; D007051:Ibotenic Acid; D013373:Substance P; D020891:Raclopride; D006220:Haloperidol; D004298:Dopamine
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