Angiotensin II is the mediator of the increase in hepatic angiotensinogen synthesis after bilateral nephrectomy.
The present study investigated the hypothesis that the increase in plasma angiotensinogen after nephrectomy is mediated by endogenous renin and angiotensin (ANG) II. Rats were divided into control, nephrectomy, or nephrectomy plus adrenalectomy groups. In addition, similar cohorts were divided as just mentioned and then given either atenolol (selective beta 1-adrenoceptor inhibitor that prevents renin release) or Dup-753 [ANG II (AT1) receptor antagonist]. The plasma angiotensinogen levels increase approximately fivefold after 24 h in nephrectomized rats. Pretreatment with atenolol blunted this increase. A significant reduction was observed 4 h (P < 0.05) and 8 h (P < 0.005) after surgery. Dup-753 nearly abolished the increase in angiotensinogen plasma levels. After pretreatment with Dup-753, significantly higher angiotensinogen levels (P < 0.005) were found only after 24 h. Nephrectomy plus adrenalectomy also blunted the rise in plasma angiotensinogen. A significant increase in angiotensinogen plasma levels could only be observed after 8 h (P < 0.005) and 12 h (P < 0.005) but not after 24 h. Atenolol further reduced this increase. After atenolol pretreatment, significantly higher angiotensinogen levels could only be observed after 12 h (P < 0.05). Dup-753 completely abolished the increase of plasma angiotensinogen after nephrectomy plus adrenalectomy. In anesthetized control rats at time 0 the plasma ANG I levels were 0.7 nM. Pretreatment with atenolol decreased the ANG I values by 30%, whereas Dup-753 caused a sixfold increase in plasma ANG I levels in the control rats at time 0.(ABSTRACT TRUNCATED AT 250 WORDS)
Hilgenfeldt
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U
Department of Pharmacology, University of Heidelberg, Germany.
Schwind
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S
D000315:Adrenalectomy; D000804:Angiotensin II / Q000502:physiology*; D000808:Angiotensinogen / Q000096:biosynthesis* / Q000097:blood; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D019808:Losartan; D008297:Male; D009392:Nephrectomy / Q000379:methods; D009994:Osmolar Concentration; D011184:Postoperative Period; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors
D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000808:Angiotensinogen; D000804:Angiotensin II; D001262:Atenolol; D012083:Renin; D019808:Losartan