Antihypertensive therapy upregulates renin and (pro)renin receptor in the clipped kidney of Goldblatt hypertensive rats.
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Antihypertensive therapy upregulates renin and (pro)renin receptor in the clipped kidney of Goldblatt hypertensive rats. / Krebs, Christian; Hamming, I; Sadaghiani, S; Steinmetz, Oliver; Meyer-Schwesinger, Catherine; Fehr, Susanne; Stahl, Rolf A.K.; Garrelds, I M; Danser, A H J; van Goor, H; Contrepas, A; Nguyen, G; Wenzel, Ulrich.
In: KIDNEY INT, Vol. 72, No. 6, 6, 2007, p. 725-730.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Antihypertensive therapy upregulates renin and (pro)renin receptor in the clipped kidney of Goldblatt hypertensive rats.
AU - Krebs, Christian
AU - Hamming, I
AU - Sadaghiani, S
AU - Steinmetz, Oliver
AU - Meyer-Schwesinger, Catherine
AU - Fehr, Susanne
AU - Stahl, Rolf A.K.
AU - Garrelds, I M
AU - Danser, A H J
AU - van Goor, H
AU - Contrepas, A
AU - Nguyen, G
AU - Wenzel, Ulrich
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 72
SP - 725
EP - 730
JO - KIDNEY INT
JF - KIDNEY INT
SN - 0085-2538
IS - 6
M1 - 6
ER -