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

Document Type: Original Article


1 Cadres Division One, The 401st Hospital of PLA, Qingdao 266071, China

2 Institute of Cardiovascular Research, Peking Medical University, First Hospital, Beijing 100083, China


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<0.01 vs. the control). However, Ang II-induced elevation of 3H-TdR incorporation, and PKC activity was significantly inhibited by various doses of ADM and PAMP (all P<0.01 vs. the Ang II group). In rat aortic vascular tissues or intubation media, Ang II treatments stimulated the expression and secretion of PAMP and ADM in a dose-dependent manner, while PAMP treatments had no significant effects on Ang II levels.
Conclusion: ADM and PAMP inhibit Ang II-induced VSMCs proliferation. The interaction of Ang II, ADM and PAMP may regulate VSMCs and cardiovascular function.



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