Acute effects of cyclooxygenase-2 inhibition on renal function in heterozygous ren-2-transgenic rats on normal or low sodium intake.

Abstract

BACKGROUND/AIMS:

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.

• Authors: Ivana Vanecková, Monika Cahová, Herbert J Kramer, Zuzana Husková, Petra Skaroupková, Radko Komers, Michael Bader, Detlev Ganten, Ludek Cervenka
• Journal: Kidney & blood pressure research (Kidney Blood Press Res) Vol. 27 Issue 4 Pg. 203-10 ( 2004) ISSN: 1420-4096 [Print] Switzerland
• PMID: 15273422 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2004 S. Karger AG, Basel

Chemical References

• Cyclooxygenase Inhibitors
• Nitrobenzenes
• Ren2 protein, mouse
• Sodium, Dietary
• Sulfonamides
• Thiophenes
• N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
• DuP 697
• Renin
• Dinoprostone

Topics

• Animals
• Animals, Genetically Modified
• Blood Pressure (drug effects)
• Cyclooxygenase Inhibitors (pharmacology)
• Diet, Sodium-Restricted
• Dinoprostone (urine)
• Glomerular Filtration Rate (drug effects)
• Kidney Cortex (drug effects, physiology)
• Male
• Nitrobenzenes (pharmacology)
• Rats
• Renal Circulation (drug effects)
• Renin (genetics)
• Renin-Angiotensin System (drug effects)
• Sodium, Dietary (pharmacology, urine)
• Sulfonamides (pharmacology)
• Thiophenes (pharmacology)