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

Ivana Vaněčková, Monika Cahová, Herbert J. Kramer, Zuzana Husková, Petra Škaroupkova, Radko Komers, Michael Bader, Detlev Ganten, Luděk Červenka

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6 Scopus citations

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 PGE 2 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.

Original languageEnglish (US)
Pages (from-to)203-210
Number of pages8
JournalKidney and Blood Pressure Research
Volume27
Issue number4
DOIs
StatePublished - Oct 7 2004

Keywords

  • Cyclooxygenase-2
  • Glomerular filtration rate
  • Hypertension
  • Renal plasma flow
  • Renin-angiotensin system
  • Sodium restriction

ASJC Scopus subject areas

  • Nephrology
  • Cardiology and Cardiovascular Medicine

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    Vaněčková, I., Cahová, M., Kramer, H. J., Husková, Z., Škaroupkova, P., Komers, R., Bader, M., Ganten, D., & Červenka, L. (2004). Acute effects of cyclooxygenase-2 inhibition on renal function in heterozygous ren-2-transgenic rats on normal or low sodium intake. Kidney and Blood Pressure Research, 27(4), 203-210. https://doi.org/10.1159/000079865