Cyclooxygenase-2 inhibition normalizes arterial blood pressure in CYP1A1-REN2 transgenic rats with inducible ANG II-dependent malignant hypertension

American Journal of Physiology. Renal Physiology
Allison L OpayKenneth D Mitchell

Abstract

The present study was performed to determine the effects of cyclooxygenase (COX)-1 and COX-2 inhibition on blood pressure and renal hemodynamics in transgenic rats with inducible malignant hypertension [strain name: TGR(Cyp1a1Ren2)]. Male Cyp1a1-Ren2 rats (n = 7) were fed a normal diet containing the aryl hydrocarbon, indole-3-carbinol (I3C; 0.3%), for 6-9 days to induce malignant hypertension. Mean arterial pressure (MAP) and renal hemodynamics were measured in pentobarbital sodium-anesthetized Cyp1a1-Ren2 rats during control conditions, following administration of the COX-2 inhibitor nimesulide (3 mg/kg iv), and following administration of the nonspecific COX inhibitor meclofenamate (5 mg/kg iv). Rats induced with I3C had higher MAP than noninduced rats (n = 7; 188 +/- 6 vs. 136 +/- 4 mmHg, P < 0.01). There was no difference in renal plasma flow (RPF) or glomerular filtration rate (GFR) between induced and noninduced rats. Nimesulide elicited a larger decrease in MAP in hypertensive rats (188 +/- 6 to 140 +/- 8 mmHg, P < 0.01) than in normotensive rats (136 +/- 4 to 113 +/- 8 mmHg, P < 0.01). Additionally, nimesulide decreased GFR (0.9 +/- 0.13 to 0.44 +/- 0.05 ml.min(-1).g(-1), P < 0.05) and RPF (2.79 +/- 0.27 to 1.35 +/- 0....Continue Reading

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Citations

Mar 25, 2009·The Journal of Biological Chemistry·Xiaojun LiuJohn J Mullins
Nov 15, 2011·Current Opinion in Nephrology and Hypertension·Torrance GreenL Gabriel Navar
Oct 14, 2011·American Journal of Physiology. Renal Physiology·Catherine G Howard, Kenneth D Mitchell
Oct 7, 2011·American Journal of Physiology. Renal Physiology·Miguel L Graciano, Kenneth D Mitchell
Jul 30, 2010·American Journal of Physiology. Renal Physiology·Torrance GreenL Gabriel Navar
Aug 21, 2010·The American Journal of the Medical Sciences·Carlo J MilaniKenneth D Mitchell
May 13, 2009·Journal of Cellular and Molecular Medicine·Barbara S PetersJörg Peters
Dec 30, 2006·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Trinity VeraDavid E Stec
Aug 22, 2014·American Journal of Physiology. Renal Physiology·Alexis A GonzalezMinolfa C Prieto
Oct 26, 2011·Journal of Hypertension·Bart F J HeijnenHarry A J Struijker-Boudier
Nov 6, 2007·American Journal of Physiology. Renal Physiology·Matthew E PattersonKenneth D Mitchell
Aug 24, 2007·American Journal of Physiology. Renal Physiology·Rudy M OrtizKenneth D Mitchell
Oct 10, 2008·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Liliana Monica BivolBjarne M Iversen

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