Angiotensin II, type 2 receptor is not involved in the angiotensin II-mediated pro-atherogenic process in ApoE-/- mice

• OBJECTIVE: Angiotensin II (Ang II) accelerates atherogenesis in ApoE mice via the angiotensin II, type 1 receptor (AT1) while the type 2 receptor (AT2) is suggested to counteract atherogenesis. To confirm and further explore this possibility, we studied the effect of AT2 receptor antagonism on Ang II-accelerated atherosclerosis. METHODS: ApoE mice were fed a standard or high cholesterol diet (1.25%) for 4 weeks. Mice on each diet were treated with either Ang II (0.5 microg/kg per min) or Ang II in combination with PD123319 (3 mg/kg per day). Plaque distribution was assessed by en face quantification of the thoracic aorta and in cross-sections of the aortic root. Mean arterial pressure (MAP) was measured. AT1 and AT2 receptor expression were analysed using real-time polymerase chain reaction (PCR) and the localization of the AT2 receptor protein confirmed with immunohistochemistry. RESULTS: Ang II infusion increased MAP only in mice on a standard diet (P < 0.001). Regardless of diet, Ang II-infused mice had 22-30 times increased plaque area in the thoracic aorta (P < 0.001 for both). Ang II had no effect on plaque in the aortic root. Plaque area was not affected by PD123319. AT2 receptor was heavily expressed in the plaques and increased six- to ninefold by a high cholesterol diet and Ang II infusion (P < 0.01). CONCLUSION: Ang II increases the extent of atherosclerosis in ApoE mice. Despite up-regulation of the AT2 receptor, we found no support for an effect of the AT2 receptor on atherogenesis in this model.

Nyckelord

Angiotensin II/*pharmacology

Animals

Aorta

Thoracic/pathology

Apolipoproteins E/*deficiency/genetics/physiology

Arteriosclerosis/*etiology/*metabolism

Blood Pressure

Cholesterol

Dietary/pharmacology

Imidazoles/pharmacology

Immunohistochemistry

Mice

Mice

Knockout

Pyridines/pharmacology

Receptor

Angiotensin

Type 2/genetics/*metabolism

Vasoconstrictor Agents/pharmacology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)