Angiotensinase activities in the kidney of renovascular hypertensive rats.
In spite of the well-known contribution of angiotensin II (Ang II) in the pathogenesis of Goldblatt two-kidney one clip (G2K1C) hypertension, the importance of other Ang peptides, such as Ang III, Ang IV or Ang 2-10, is scarcely understood. The functional status of these peptides depends on the action of several aminopeptidases called angiotensinases. The metabolism of Ang III to Ang IV by aminopeptidase M (AlaAP) and of Ang I to Ang 2-10 by aspartyl aminopeptidase (AspAP) was evaluated in the renal cortex and medulla of normotensive (Sham-operated) and hypertensive (G2K1C) rats, treated or not with the AT(1) receptor antagonist valsartan. The results demonstrated a highly significant increase of membrane-bound (MEMB) AlaAP in the cortex of the non-ischemic kidney of G2K1C rats compared with the kidney of normal rats and with the clipped kidney of G2K1C rats. This suggests an increased formation of Ang IV in the non-clipped kidney of G2R1C rats. Valsartan reduced MEMB AlaAP and AspAP activities in the renal cortex of normotensive and in the clipped kidney of hypertensive rats. The reduced metabolism of Ang III may prolong its half-life in valsartan-treated animals. These results suggest a role for AlaAP in renovascular hypertension. In addition, the higher AspAP activity of the renal cortex compared to medulla reflects its relative functional difference between both locations.
Prieto
Isabel
I
Unit of Physiology, University of Jaén, Bldg B-3, 23071 Jaén, Spain.
Hermoso
Francisco
F
Gasparo
Marc de
Md
Vargas
Félix
F
Alba
Francisco
F
Segarra
Ana B
AB
Banegas
Inmaculada
I
Ramírez
Manuel
M
D000302:Adrenal Cortex / Q000166:cytology; D000313:Adrenal Medulla / Q000166:cytology; D000626:Aminopeptidases / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D018826:CD13 Antigens / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology; D010450:Endopeptidases / Q000378:metabolism*; D043384:Glutamyl Aminopeptidase / Q000378:metabolism; D006978:Hypertension, Renovascular / Q000201:enzymology*; D007668:Kidney / Q000166:cytology / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D013777:Tetrazoles; C076819:angiotensinase; D000068756:Valsartan; D010450:Endopeptidases; D000626:Aminopeptidases; D018826:CD13 Antigens; D043384:Glutamyl Aminopeptidase; D014633:Valine