title: Effects of angiotensin II and the AT(1) receptor antagonist losartan on the renal excretion of urodilatin.
abstract: BACKGROUND
  The precise mechanisms regulating the natriuretic peptide urodilatin (ANP-95-126) remain to be defined. Renal excretion of urodilatin (U(URO)V) has been shown to be modified by variations in plasma sodium and renal perfusion pressure. This suggests a relationship between urodilatin and the renin-angiotensin system.
  
  
  METHODS
  We investigated the effects of angiotensin II (AII, 0.1 nmol/l) and the AT(1) receptor antagonist losartan (LS, 1 micromol/l) on U(URO)V and renal function in isolated rat kidneys perfused for 180 min in a closed circuit system. A further series employing a vasoconstricting concentration of endothelin-1 (ET-1, 0.01 nmol/l) was performed to explore the effects of vasoconstriction and glomerular filtration rate (GFR) on U(URO)V.
  
  
  RESULTS
  Urine flow (UV) and urinary sodium excretion (U(Na)V) decreased and renal vascular resistance (RVR) increased after treatment with AII (n = 5) in comparison with a control group (n = 6; p < 0.05). Treatment with LS (n = 5) and AII+LS (n = 5) had no significant effect on these parameters. GFR decreased after AII (p < 0.05) and was not significantly altered by other interventions. U(URO)V decreased after AII (p < 0.05) and was comparable to the control group after LS and AII+LS. ET-1 (n = 5) induced a significant increase in RVR and decreased UV and U(Na)V (p < 0.05). Point-to-point analysis revealed that the ET-1-induced vasoconstriction and the subsequent decrease in GFR had no effect on U(URO)V.
  
  
  CONCLUSIONS
  This suggests that vasoconstrictory concentrations of AII decrease U(URO)V in the isolated perfused rat kidney. The lack of effect of ET-1 on U(URO)V suggests that the AII-induced alterations in urodilatin excretion cannot be explained by vasoconstriction per se.
authors: Klinik für Anaesthesiologie, Medizinische Universität zu Lübeck, Deutschland. Heringlake@t-online.de
authors: M
authors: M
authors: Heringlake
authors: L
authors: L
authors: Bahlmann
authors: S
authors: S
authors: Klaus
authors: K
authors: K
authors: Wagner
authors: P
authors: P
authors: Schmucker
authors: H
authors: H
authors: Pagel
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000652:urine*; D019332:Endothelin-1 / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D010446:Peptide Fragments / Q000652:urine*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D057911:Angiotensin Receptor Antagonists; D019332:Endothelin-1; D010446:Peptide Fragments; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C056452:Ularitide; D009320:Atrial Natriuretic Factor; D012964:Sodium; D019808:Losartan