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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Physiol+Renal+Physiol
2014 ; 307
(8
): F962-70
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English Wikipedia
Renal medullary cyclooxygenase-2 and (pro)renin receptor expression during
angiotensin II-dependent hypertension
#MMPMID25143455
Gonzalez AA
; Green T
; Luffman C
; Bourgeois CR
; Gabriel Navar L
; Prieto MC
Am J Physiol Renal Physiol
2014[Oct]; 307
(8
): F962-70
PMID25143455
show ga
The (pro)renin receptor [(P)RR] upregulates cyclooxygenase-2 (COX-2) in inner
medullary collecting duct (IMCD) cells through ERK1/2. Intrarenal COX-2 and (P)RR
are upregulated during chronic ANG II infusion. However, the duration of COX-2
and (P)RR upregulation has not been determined. We hypothesized that during the
early phase of ANG II-dependent hypertension, membrane-bound (P)RR and COX-2 are
augmented in the renal medulla, serving to buffer the hypertensinogenic and
vasoconstricting effects of ANG II. In Sprague-Dawley rats infused with ANG II
(0.4 ?g·min(-1)·kg(-1)), systolic blood pressure (BP) increased by day 7 (162 ± 5
vs. 114 ± 10 mmHg) and continued to increase by day 14 (198 ± 15 vs. 115 ± 13
mmHg). Membrane-bound (P)RR was augmented at day 3 coincident with phospho-ERK1/2
levels, COX-2 expression, and PGE2 in the renal medulla. In contrast,
membrane-bound (P)RR was reduced and COX-2 protein levels were not different from
controls by day 14. In cultured IMCD cells, ANG II increased secretion of the
soluble (P)RR. In anesthetized rats, COX-2 inhibition decreased the glomerular
filtration rate (GFR) and renal blood flow (RBF) during the early phase of ANG II
infusion without altering BP. However, at 14 days of ANG II infusions, COX-2
inhibition decreased mean arterial BP (MABP), RBF, and GFR. Thus, during the
early phase of ANG II-dependent hypertension, the increased (P)RR and COX-2
expression in the renal medulla may contribute to attenuate the vasoconstrictor
effects of ANG II on renal hemodynamics. In contrast, at 14 days the reductions
in RBF and GFR caused by COX-2 inhibition paralleled the reduced MABP, suggesting
that vasoconstrictor COX-2 metabolites contribute to ANG II hypertension.