Angiotensin II stimulates cyclooxygenase-2 mRNA expression in renal tissue from rats with kidney failure.
We have shown increased cyclooxygenase-2 (COX-2) expression in rats with kidney failure. Increased angiotensin II concentration, hypertension, and renal mass reduction have been described during development of kidney failure. Thus we explored each of these mechanisms, because any one of them could be responsible for COX-2 induction. Kidney failure increased systolic blood pressure from 104 +/- 5 to 138 +/- 2 mmHg, urinary PGE(2) from 74 +/- 17 to 185 +/- 25 ng/24 h, and COX-2 expression from 0.06 +/- 0.04 to 0.17 +/- 0.03 arbitraty units (AU). Treatment of the rats with ramipril or losartan prevented the increase in blood pressure, urinary PGE(2), and COX-2 expression in the rats with kidney failure. Infusion of angiotensin II increased blood pressure from 101 +/- 6 to 132 +/- 6 mm Hg, urinary PGE(2) excretion from 62 +/- 15 to 155 +/- 17 ng/24 h, and COX-2 expression from 0.23 +/- 0.01 to 1.6 +/- 0.3 AU. When the angiotensin II-infused rats were treated with nitrendipine, blood pressure decreased from 132 +/- 6 to 115 +/- 2 mm Hg, and urinary PGE(2) excretion decreased from 152 +/- 18 to 97 +/- 12 ng/24 h, whereas COX-2 expression was 1.6 +/- 0.7 and 1.7 +/- 0.5 AU for rats with and without nitrendipine. Blood pressure of the rats with renal pole resection was similar to that in sham rats (97 +/- 7 and 91 +/- 4 mmHg, respectively), whereas COX-2 expression was increased in rats with renal pole resection, from 0.06 +/- 0.04 to 0.12 +/- 0.03 AU. We suggest that in kidney failure, the increase in angiotensin II concentration regulates COX-2 expression, thereby increasing prostaglandin synthesis, which contributes to the development of kidney failure.
Hernández
José
J
Department of Pharmacology, Mexico City CP07300, Mexico.
Astudillo
Horacio
H
Escalante
Bruno
B
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D051546:Cyclooxygenase 2; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis*; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D009392:Nephrectomy; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D051437:Renal Insufficiency / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013268:Stimulation, Chemical
D000959:Antihypertensive Agents; D007527:Isoenzymes; D012333:RNA, Messenger; D000804:Angiotensin II; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases