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. 2016 Jan;19(1):49-54.

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

Jian Ma  1 , Yinglu Feng  1 , Zaiquan Li  2 , Chaoshu Tang  2
Affiliations

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

Jian Ma et al. Iran J Basic Med Sci. 2016 Jan.

Abstract

Objectives: The study aimed to investigate the effects of adrenomedullin (ADM) and proadrenomedullin N- terminal 20 peptide (PAMP) on angiotensin (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 (3)H-TdR incorporation. Protein kinase C (PKC) activity was measured by counting γ-(32)P 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 (3)H-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 (3)H-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.

Keywords: Adrenomedulin; Angiotension II; Proadrenomedullin N-terminal 20 peptide; Proliferation; Vascular smooth muscle-cell.

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Figures

Figure 1
Figure 1
A. The effect of different doses of angiotensin II (Ang II) on secreted proadrenomedullin N- terminal 20 peptide (PAMP) levels in the intubation medium. B. The effect of Ang II on the tissue concentrations of PAMP and adrenomedullin (ADM). C. The effect of AngII on the tissue and incubation concentrations of PAMP and ADM (PAMP/ADM). Data were presented as mean ± SEM; n=6. *P<0.01 vs. control
Figure 2
Figure 2
The effect of proadrenomedullin N- terminal 20 peptide (PAMP) on the tissue and incubation concentrations of angiotensin II (Ang II). Data were presented as mean ± SEM; n=6. *P<0.05 vs. control
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