Chronic cyclooxygenase-2 inhibition does not alter blood pressure and kidney function in renovascular hypertensive rats.
BACKGROUND
It has been shown that the macula densa participates in the regulation of increased renin expression in two-kidney one-clip (2K1C) renovascular hypertension. Prostaglandins might be one of the mediators of macula densa function, because the cyclooxygenase-2 (COX-2), one of the rate-limiting enzymes of the prostaglandin pathway, is upregulated in 2K1C renovascular hypertensive rats. We tested the effect of chronic COX-2 inhibition on blood pressure, urinary aldosterone excretion and kidney morphology, as well as kidney function.


METHODS
Four groups were established: two groups of 2K1C renovascular hypertensive rats treated with the specific COX-2 inhibitor Celecoxib (cele) (15 mg/kg per day) or placebo immediately after operation, and two sham-operated control groups fed with Celecoxib or placebo.


RESULTS
Long-term COX-2 inhibition in 2K1C renovascular hypertensive rats did not alter blood pressure at any point of time. Urinary aldosterone excretion was elevated by clipping the renal artery (2K1C, 8.1 +/- 1.9, versus controls, 3.6 +/- 0.5 ng/24 h; P = 0.05) but was not influenced by treatment with Celecoxib. Also, Celecoxib treatment did not alter glomerular filtration rate (GFR), serum sodium, serum creatinine, serum urea or proteinuria in 2K1C renovascular hypertensive rats. Interstitial fibrosis of the left clipped kidney was markedly reduced (2K1C, 6.19 +/- 0.83% versus 2K1C + cele 3.00 +/- 0.68% of total area; P = 0.012), whereas the interstitial fibrosis of the non-clipped kidney or the glomerulosclerosis of both kidneys were not affected by Celecoxib treatment.


CONCLUSIONS
Celecoxib reduces the interstitial fibrosis of the clipped kidney. Blood pressure, urinary aldosterone excretion or whole kidney function were not affected in renal hypertensive rats.
Richter
Claus M
CM
Center for Cardiovascular Research, Charité, Humboldt University of Berlin, Germany.
Godes
Michael
M
Wagner
Charlotte
C
Maser-Gluth
Christiane
C
Herzfeld
Sophia
S
Dorn
Maren
M
Priem
Friedrich
F
Slowinski
Torsten
T
Bauer
Christian
C
Schneider
Wolfgang
W
Neumayer
Hans H
HH
Kurtz
Armin
A
Hocher
Berthold
B
D000450:Aldosterone / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001794:Blood Pressure / Q000187:drug effects*; D000068579:Celecoxib; D003404:Creatinine / Q000097:blood; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000378:metabolism* / Q000503:physiopathology*; D007527:Isoenzymes / Q000187:drug effects* / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism / Q000502:physiology*; D008297:Male; D023421:Models, Animal; D008955:Models, Cardiovascular; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects* / Q000378:metabolism*; D011720:Pyrazoles; D051381:Rats; D011921:Rats, Inbred WKY; D012083:Renin / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D013599:Systole / Q000187:drug effects; D013997:Time Factors; D014508:Urea / Q000097:blood
D015415:Biomarkers; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D011720:Pyrazoles; D013449:Sulfonamides; D000450:Aldosterone; D014508:Urea; D003404:Creatinine; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D012083:Renin; D000068579:Celecoxib