Antihypertensive therapy upregulates renin and (pro)renin receptor in the clipped kidney of Goldblatt hypertensive rats.
Recently, a (pro)renin receptor has been identified which mediates profibrotic effects independent of angiotensin II. Because antihypertensive therapy induces renal injury in the clipped kidney of two kidney-1-clip hypertensive rats, we examined the regulation of renin and the (pro)renin receptor in this model. Hypertensive Goldblatt rats were treated with increasing doses of the vasopeptidase inhibitor AVE 7688 after which the plasma renin and prorenin as well as the renal renin and (pro)renin receptor expression were measured. The vasopeptidase inhibitor dose-dependently lowered blood pressure, which was associated with a massive increase in plasma prorenin and renin as well as increased renal renin expression. The (pro)renin receptor was upregulated in the clipped kidney of the Goldblatt rat indicating a parallel upregulation of renin and its receptor in vivo. Immunohistochemistry showed a redistribution of renin upstream from the glomerulus in preglomerular vessels and renin staining in tubular cells. Expression of the (pro)renin receptor was increased in the vessels and tubules. This upregulation was associated with thickening of renin-positive vessels and tubulointerstitial damage. We propose that renin and the (pro)renin receptor may play a profibrotic role in the clipped kidney of Goldblatt rats treated for hypertension.
Krebs
C
C
Division of Nephrology, Department of Medicine, University Hospital of Hamburg, Hamburg, Germany.
Hamming
I
I
Sadaghiani
S
S
Steinmetz
O M
OM
Meyer-Schwesinger
C
C
Fehr
S
S
Stahl
R A K
RA
Garrelds
I M
IM
Danser
A H J
AH
van Goor
H
H
Contrepas
A
A
Nguyen
G
G
Wenzel
U
U
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology*; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D011355:Prodrugs / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012083:Renin / Q000378:metabolism*; D013525:Surgical Instruments; D015854:Up-Regulation / Q000187:drug effects; D000093342:Prorenin Receptor
C479877:AVE 7688; D006575:Heterocyclic Compounds, 3-Ring; D011355:Prodrugs; D011956:Receptors, Cell Surface; D012083:Renin; D000093342:Prorenin Receptor