In:
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, American Physiological Society, Vol. 298, No. 4 ( 2010-04), p. R1017-R1025
Abstract:
Inhibitors of cyclooxygenase (COX)-2 prevent suppression of aquaporin-2 and reduce polyuria in the acute phase after release of bilateral ureteral obstruction (BUO). We hypothesized that BUO leads to COX-2-mediated local accumulation of prostanoids in inner medulla (IM) tissue. To test this, rats were subjected to BUO and treated with selective COX-1 or COX-2 inhibitors. Tissue was examined at 2, 6, 12, and 24 h after BUO. COX-2 protein abundance increased in IM 12 and 24 h after onset of BUO but did not change in cortex. COX-1 did not change at any time points in any region. A full profile of all five primary prostanoids was obtained by mass spectrometric determination of PGE 2 , PGF 2α , 6-keto-PGF 1α , PGD 2 , and thromboxane (Tx) B 2 concentrations in kidney cortex/outer medulla and IM fractions. IM concentration of PGE 2 , 6-keto-PGF 1α , and PGF 2α was increased at 6 h BUO, and PGE 2 and PGF 2α increased further at 12 h BUO. TxB 2 increased after 12 h BUO. 6-keto-PGF 1α remained significantly increased after 24 h BUO. The COX-2 inhibitor parecoxib lowered IM PGE 2, TxB 2 , 6-keto-PGF 1α , and PGF 2α below vehicle-treated BUO and sham rats at 6, 12 and, 24 h BUO. The COX-1 inhibitor SC-560 lowered PGE 2 , PGF 2α , and PGD 2 in IM compared with untreated 12 h BUO, but levels remained significantly above sham. In cortex tissue, PGE 2 and 6-keto-PGF 1α concentrations were elevated at 6 h only. In conclusion, COX-2 activity contributes to the transient increase in prostacyclin metabolite 6-keto-PGF 1α and TxB 2 concentration in the kidney IM, and COX-2 is the predominant isoform that is responsible for accumulation of PGE 2 and PGF 2α with minor, but significant, contributions from COX-1. PGD 2 synthesis is mediated exclusively by COX-1. In BUO, therapeutic interventions aimed at the COX-prostanoid pathway should target primarily COX-2.
Type of Medium:
Online Resource
ISSN:
0363-6119
,
1522-1490
DOI:
10.1152/ajpregu.00336.2009
Language:
English
Publisher:
American Physiological Society
Publication Date:
2010
detail.hit.zdb_id:
1477297-8
SSG:
12
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