Acute effects of cyclooxygenase-2 inhibition on renal function in heterozygous ren-2-transgenic rats on normal or low sodium intake.
OBJECTIVE
Since there are no data available so far on the role of renal cyclooxygenase-2 (COX-2) in hypertensive Ren-2-transgenic rats (TGR), in the present study we evaluated renal cortical COX-2 protein expression and prostaglandin E2 (PGE2) concentrations as well as renal functional responses to acute COX-2 inhibition in male heterozygous TGR and in normotensive Hannover Sprague-Dawley (HanSD) rats fed either a normal-sodium (NS) or a low-sodium (LS) diet.


METHODS
In rats fed either the NS or the LS diet for 12 days and prepared for clearance experiments with left ureteral catheterization, the renal functional responses of the left kidney were evaluated after intrarenal COX-2 inhibition with DuP-697 or NS-398. In renal cortical tissue, COX-2 protein expression was assessed by immunoblotting, and the concentration of PGE2 as a marker of COX-2 activity was determined by enzyme immunoassay. Mean arterial pressure in the right femoral artery was monitored by means of a pressure transducer.


RESULTS
In heterozygous TGR, to our surprise, the LS diet normalized the mean arterial pressure. Despite significantly higher renocortical expression of COX-2 and PGE2 concentrations as well as urinary PGE2 excretion in TGR as compared with HanSD rats kept on the NS diet, selective intrarenal COX-2 inhibition did not influence renal function either in TGR or in HanSD rats. The LS diet increased renocortical COX-2 expression and PGE2 concentrations as well as urinary PGE2 excretion significantly stronger in TGR than in HanSD rats. Regardless of these increases, the intrarenal COX-2 inhibition caused comparable decreases in glomerular filtration rate, in absolute and fractional sodium excretion, as well as in urinary PGE2 excretion in TGR and HanSD rats kept on the LS diet.


CONCLUSIONS
The present data show that a LS diet normalizes the mean arterial pressure in heterozygous male TGR. This first study on the role of renal COX-2 in TGR also demonstrates that COX-2-derived vasodilatory prostanoids do not act as renal compensatory vasodilator and natriuretic substances in this model of hypertension.
Vanecková
Ivana
I
Center of Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Cahová
Monika
M
Kramer
Herbert J
HJ
Husková
Zuzana
Z
Skaroupková
Petra
P
Komers
Radko
R
Bader
Michael
M
Ganten
Detlev
D
Cervenka
Ludek
L
D000818:Animals; D030801:Animals, Genetically Modified; D001794:Blood Pressure / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004039:Diet, Sodium-Restricted; D015232:Dinoprostone / Q000652:urine; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007672:Kidney Cortex / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009578:Nitrobenzenes / Q000494:pharmacology; D051381:Rats; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000187:drug effects; D012982:Sodium, Dietary / Q000494:pharmacology* / Q000652:urine; D013449:Sulfonamides / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; C473112:Ren2 protein, mouse; D012982:Sodium, Dietary; D013449:Sulfonamides; D013876:Thiophenes; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; C064874:DuP 697; D012083:Renin; D015232:Dinoprostone