Expression of Cell Cycle Proteins in Blood Vessels of Angiotensin II–Infused Rats

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Abstract
Angiotensin II is an important modulator of cell growth through AT 1 receptors, as demonstrated both in vivo and in vitro. We investigated the role of proteins involved in the cell cycle, including cyclin D1, cyclin-dependent kinase 4 (cdk4), and cyclin-dependent kinase inhibitors p21 and p27 in blood vessels of angiotensin II–infused rats and the effect therein of the AT 1 -receptor antagonist losartan. Male Sprague-Dawley rats were infused for 7 days with angiotensin II (120 ng/kg per minute SC) and/or treated with losartan (10 mg/kg per day orally). DNA synthesis in mesenteric arteries was evaluated by radiolabeled 3 H-thymidine incorporation. The expression of cyclin D1, cdk4, p21, and p27, which play critical roles during the G 1 -phase of the cell cycle process, was examined by Western blot analysis. Tail-cuff systolic blood pressure (mm Hg) was elevated ( P 3 H-thymidine incorporation (cpm/100 μg DNA) showed that angiotensin II infusion significantly increased DNA synthesis (152±5% versus 102±6% of control rats, P 1 receptors are stimulated in vivo, DNA synthesis is enhanced in blood vessels by activation of cyclin D1 and cdk4. Reduction in cell cycle kinase inhibitors p21 and p27 may contribute to activation of growth induced by in vivo AT 1 receptor stimulation.