title: Vascular effects of a tripeptide fragment of novokinine in hypertensive rats: Mechanism of the hypotensive action.
abstract: BACKGROUND
  Activation of angiotensin AT2 receptors (AT2R) counteracts vasoconstrictor effects of AT1R stimulation and contributes to blood pressure control. We examined effects on mean arterial pressure (MAP) and renal hemodynamics of LKP, a tripeptide fragment of novokinine, an established AT2R agonist.
  
  
  METHODS
  Effects of intravenous LKP infusion and then superimposed losartan (AT1R antagonist) on MAP, total renal (RBF, Transonic probe) and renal medullary blood flows (laser-Doppler), and on renal excretion, were examined in anesthetized (1) Wistar rats with acute norepinephrine-induced hypertension, untreated or pretreated with AT2R antagonist (PD 123319) and (2) spontaneously hypertensive rats (SHR) maintained on standard or high-sodium (HS) diet.
  
  
  RESULTS
  In Wistar rats LKP decreased MAP (-4%, p<0.01) and increased renal medullary perfusion, these effects were abolished in rats pretreated with PD 123319 in which a post-LKP increase in MAP (+6%, p<0.02) occurred. LKP did not alter MAP in SHR; in those on HS diet RBF decreased (-14%, p<0.02), the response that was reverted by losartan. Addition of losartan always decreased or tended to decrease MAP.
  
  
  CONCLUSIONS
  LKP lowered MAP in norepinephrine-induced hypertension, probably via activation of AT2R. At reduced availability of AT2R, as in SHR, LKP appeared to bind to different receptors, possibly AT1, and induced systemic or renal vasoconstriction. Compared to the parent novokinine, a smaller LKP molecule might be easier absorbed after oral application and more useful in therapy.
authors.affiliation: Department of Renal and Body Fluid Physiology, Mossakowski Medical Reasearch Center Polish Academy of Sciences, Warszawa, Poland. Electronic address: bbadzynska@imdik.pan.pl.
authors.forename: Bożena
authors.initials: B
authors.lastname: Bądzyńska
authors.affiliation: Department of Neuropeptides, Mossakowski Medical Reasearch Center Polish Academy of Sciences, Warszawa, Poland.
authors.forename: Andrzej W
authors.initials: AW
authors.lastname: Lipkowski
authors.affiliation: Department of Renal and Body Fluid Physiology, Mossakowski Medical Reasearch Center Polish Academy of Sciences, Warszawa, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Sadowski
authors.affiliation: Department of Renal and Body Fluid Physiology, Mossakowski Medical Reasearch Center Polish Academy of Sciences, Warszawa, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Kompanowska-Jezierska
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology; D007262:Infusions, Intravenous; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D044139:Receptor, Angiotensin, Type 2 / Q000187:drug effects / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; C511871:Arg-Pro-Leu-Lys-Pro-Trp; D007093:Imidazoles; D009842:Oligopeptides; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; C000597540:leucyl-lysyl-proline; C073402:PD 123319; D019808:Losartan; D009638:Norepinephrine
keywords: AT(1) receptor blocker; AT(2) receptor blocker; Angiotensin II; Blood pressure; Kidney hemodynamics