The effect of adrenomedullin and proadrenomedullin N- terminal 20 peptide on angiotensin II induced vascular smooth muscle cell proliferation

Objective(s): The study aimed to investigate the effects of adrenomedullin (ADM) and proadrenomedullin N- terminal 20 peptide (PAMP) on angiotensin II (AngII)-stimulated proliferation in vascular smooth muscle cells (VSMCs). Materials and Methods: Thoracic aorta was obtained from Wistar rats and VSMCs were isolated from aorta tissues and then cultured. In vitro cultured VSMCs were stimulated with Ang II (10-8 mol/l) followed by various doses of PAMP or ADM (10-9, 10-8, or 10-7 mol/l). Cell proliferation as assessed by 3H-TdR incorporation. Protein kinase C (PKC) activity was measured by counting γ-32P radioactivity with liquid scintillation. In a separate cohort, in vitro cultured rat aortic vessels were treated with different doses of Ang II or PAMP (10-9, 10-8, or 10-7 mol/l). Cellular and secreted levels of PAMP, ADM and Ang II were measured using radioimmunoassay in the tissues and intubation mediums, respectively. Results: Ang II (10-8 mol/l) treatment significantly increased both 3H-TdR incorporation and PKC activity in VSMCs (by 2.68 and 1.02-fold, respectively; both P