COX-2 inhibition potentiates the antiproteinuric effect of enalapril in uninephrectomized SHR.
PGE(2) and PGI(2) reduce extracellular matrix deposition and their production is altered after ACE inhibitor (ACEi) treatment. We therefore hypothesized that cyclooxygenase (COX)-2 inhibition would exacerbate renal injury and antagonize the effects of ACEi. To test these hypotheses, WKY and SHR were uninephrectomized (UNX) and treated with either vehicle, enalapril, NS398 or enalapril+NS398. NS398 did not affect systolic blood pressure nor antagonize the antihypertensive effect of enalapril. Urinary protein excretion in UNX WKY was significantly decreased after treatment with either enalapril or NS398. In UNX SHR, enalapril reduced proteinuria, but NS398 alone had no effect. Administration of both drugs, however, further reduced proteinuria. In UNX WKY, treatment with either NS398 alone or both drugs reduced glomerular volume and similar results were observed in SHR. Surprisingly, these results disprove our original hypothesis and suggest that inhibition of COX-2 provides additional renoprotection to that of enalapril alone.
Harding
Pamela
P
Department of Pathology and Anatomy, Eastern Virginia Medical School, 700 Olney Road, Norfolk, VA 23501, USA. hardinp@evmsmail.evms.edu
Glass
William F
WF
Scherer
Steven D
SD
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure; D001835:Body Weight; D024043:Collagen Type II / Q000378:metabolism; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004656:Enalapril / Q000494:pharmacology*; D006984:Hypertrophy / Q000473:pathology; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000502:physiology; D007674:Kidney Diseases / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D008297:Male; D009392:Nephrectomy; D009578:Nitrobenzenes / Q000494:pharmacology; D009929:Organ Size; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D011453:Prostaglandins / Q000652:urine; D011507:Proteinuria / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013449:Sulfonamides / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D024043:Collagen Type II; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D009578:Nitrobenzenes; D011453:Prostaglandins; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D004656:Enalapril; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases