Telmisartan prevents aneurysm progression in the rat by inhibiting proteolysis, apoptosis and inflammation.

Abstract

OBJECTIVES:

We investigated the effects of treatment with the angiotensin II type 1 receptor antagonist, telmisartan, on abdominal aortic aneurysm formation in normotensive rats.

METHODS:

Abdominal aortic aneurysm was induced by perfusion of an isolated aortic segment with elastase. Treatment with telmisattan (0.5 mg/kg per day) or hydralazine (15 mg/kg per day) was started after surgery and continued for 14 days. Sham-operated animals and vehicle-treated animals after aneurysm induction served as controls. Aortic diameter was measured using ultrasound before aneurysm induction and on days 7 and 14 after aneurysm induction.

RESULTS:

On day 14, aortic diameter was increased two-fold in the vehicle-treated group compared to sham-operated animals (2.02 +/- 0.12 vs. 0.87 +/- 0.02 mm, P < 0.005, n = 8). Telmisartan treatment significantly reduced aneurysmal size (1.65 +/- 0.06 vs. 2.02 +/- 0.12 mm in vehicle, P < 0.05, n = 8), whereas treatment with hydralazine had no effect. Matrix metallopeptidase 3, cathepsin D, nuclear factor kappa B, tumour necrosis factor alpha, transforming growth factor-1 beta, as well as caspase 3, p53 and Fas ligand proteins, were significantly downregulated in aortic tissue under telmisartan compared to vehicle treatment. Serum monocyte chemoattractant protein 1 levels were also significantly decreased. Telmisartan and hydralazine reduced blood pressure to a similar extent within the observation period.

CONCLUSION:

The angiotensin II type 1 receptor antagonist, telmisartan, prevents abdominal aortic aneurysm progression independently of blood pressure reduction by inhibiting proteolysis, apoptosis and inflammation in aortic tissue.

• Authors: Elena Kaschina, Felix Schrader, Manuela Sommerfeld, Ulrich Rudolf Kemnitz, Aleksandra Grzesiak, Maxim Krikov, Thomas Unger
• Journal: Journal of hypertension (J Hypertens) Vol. 26 Issue 12 Pg. 2361-73 (Dec 2008) ISSN: 0263-6352 [Print] England
• PMID: 19008714 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Antihypertensive Agents
• Benzimidazoles
• Benzoates
• NF-kappa B
• Tumor Necrosis Factor-alpha
• Hydralazine
• Cathepsin D
• Matrix Metalloproteinase 3
• Telmisartan

Topics

• Angiotensin II Type 1 Receptor Blockers (pharmacology)
• Animals
• Antihypertensive Agents (pharmacology)
• Aorta, Abdominal (drug effects, pathology, physiopathology)
• Aortic Aneurysm, Abdominal (pathology, physiopathology, prevention & control)
• Apoptosis (drug effects)
• Benzimidazoles (pharmacology)
• Benzoates (pharmacology)
• Blood Pressure (drug effects)
• Cathepsin D (metabolism)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Hydralazine (pharmacology)
• Inflammation (pathology, physiopathology, prevention & control)
• Male
• Matrix Metalloproteinase 3 (metabolism)
• NF-kappa B (metabolism)
• Protein Denaturation (drug effects)
• Rats
• Rats, Inbred BN
• Telmisartan
• Tumor Necrosis Factor-alpha (metabolism)