title: Which factor mediates reno-renal control of renin gene expression?
abstract: OBJECTIVE
  To obtain information about possible pathways mediating the suppression of renin gene expression in the contralateral kidneys of stenosed kidneys.
  
  
  METHODS
  The effects of unilateral renal denervation and of treatment with an angiotensin II antagonist (losartan) on renal renin gene expression were examined in a two-kidney, one-clip model.
  
  
  METHODS
  Renal renin messenger RNA levels, plasma renin activity, blood pressure and kidney weights were monitored over 10 days in adult male Sprague-Dawley rats with various unilateral reductions of renal blood flow achieved with silver clips of 0.2, 0.3 and 0.4 mm inner diameter.
  
  
  RESULTS
  With all the clip sizes used, renin messenger RNA levels increased transiently in the clipped kidneys, the time course and the magnitude of the increase being dependent on the degree of flow reduction. In the contralateral kidneys clipping caused sustained decreases in renin messenger RNA to levels proportional to the clip size. The suppression of renin gene expression in the contralateral kidneys was not related to compensatory growth of the organs nor to changes in plasma renin activity or arterial pressure. Unilateral denervation of the kidney before clipping had no influence on the characteristic increase and decrease in renin messenger RNA in the stenosed and contralateral kidneys, respectively. Treatment of the rats with losartan led to fourfold increases in renal renin messenger RNA levels and to sixfold increases in plasma renin activity in control rats. A 0.3-mm clip did not further increase renin messenger RNA or plasma renin activity in losartan-treated rats but again led to suppression of renin messenger RNA in the contralateral kidney to 50% of the levels found in the clipped kidneys.
  
  
  CONCLUSIONS
  The results suggest that the suppression of renin gene expression in the contralateral kidneys of stenosed kidneys is not due to compensatory renal growth nor mediated by systemic blood pressure, angiotensin II AT1 receptors or renal nerves. We therefore hypothesize that kidneys with reduced perfusion release a humoral factor that acts as a potent inhibitor of renin gene expression.
authors.affiliation: Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Holmer
authors.forename: K U
authors.initials: KU
authors.lastname: Eckardt
authors.forename: O
authors.initials: O
authors.lastname: Aedtner
authors.forename: M
authors.initials: M
authors.lastname: LeHir
authors.forename: K
authors.initials: K
authors.lastname: Schricker
authors.forename: M
authors.initials: M
authors.lastname: Hamann
authors.forename: K
authors.initials: K
authors.lastname: Götz
authors.forename: G
authors.initials: G
authors.lastname: Riegger
authors.forename: W
authors.initials: W
authors.lastname: Moll
authors.forename: A
authors.initials: A
authors.lastname: Kurtz
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D003250:Constriction; D003714:Denervation; D005786:Gene Expression Regulation; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000294:innervation / Q000378:metabolism / Q000502:physiology*; D019808:Losartan; D008297:Male; D009424:Nervous System Physiological Phenomena; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012077:Renal Artery / Q000502:physiology; D012079:Renal Circulation / Q000502:physiology; D012083:Renin / Q000097:blood / Q000235:genetics*; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D012333:RNA, Messenger; D013777:Tetrazoles; D012083:Renin; D019808:Losartan