Related Experiment Videos
Angiotensin II stimulates cyclooxygenase-2 mRNA expression in renal tissue from rats with kidney failure
José Hernández1, Horacio Astudillo, Bruno Escalante
1Department of Pharmacology, Mexico City CP07300, Mexico.
Abstract:
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.
Insights
Kidney failure increases cyclooxygenase-2 (COX-2) expression in rats. Angiotensin II concentration, not hypertension or reduced kidney mass, appears to regulate this COX-2 increase and subsequent prostaglandin synthesis, contributing to kidney failure.
Area of Science:
- Nephrology
- Molecular Biology
- Cardiovascular Physiology
Background:
- Kidney failure is associated with increased cyclooxygenase-2 (COX-2) expression.
- Potential mechanisms include elevated angiotensin II, hypertension, and reduced renal mass.
Purpose of the Study:
- To investigate the role of angiotensin II, hypertension, and renal mass reduction in COX-2 induction during kidney failure.
- To determine the impact of angiotensin II on prostaglandin synthesis and COX-2 expression.
Main Methods:
- Rats with kidney failure were analyzed for blood pressure, urinary prostaglandin E2 (PGE2), and COX-2 expression.
- Interventions included ramipril, losartan, angiotensin II infusion, and nitrendipine treatment.
- Renal pole resection was performed to model reduced renal mass.
Main Results:
- Kidney failure increased blood pressure, urinary PGE2, and COX-2 expression.
- Ramipril and losartan mitigated these increases.
- Angiotensin II infusion significantly elevated blood pressure, PGE2, and COX-2 expression.
- Nitrendipine reduced blood pressure and PGE2 but not COX-2 in angiotensin II-infused rats.
- Renal pole resection increased COX-2 but not blood pressure.
Conclusions:
- Increased angiotensin II concentration, rather than hypertension or reduced renal mass, is the primary regulator of COX-2 expression in kidney failure.
- Angiotensin II-mediated COX-2 induction contributes to increased prostaglandin synthesis, potentially exacerbating kidney failure.