The effect of adrenomedullin and proadrenomedullin N- terminal ۲۰ 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 ۲۰ 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 (۱۰-۸ mol/l) followed by various doses of PAMP or ADM (۱۰-۹, ۱۰-۸, or ۱۰-۷ mol/l). Cell proliferation as assessed by ۳H-TdR incorporation. Protein kinase C (PKC) activity was measured by counting γ-۳۲P radioactivity with liquid scintillation. In a separate cohort, in vitro cultured rat aortic vessels were treated with different doses of Ang II or PAMP (۱۰-۹, ۱۰-۸, or ۱۰-۷ 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 (۱۰-۸ mol/l) treatment significantly increased both ۳H-TdR incorporation and PKC activity in VSMCs (by ۲.۶۸ and ۱.۰۲-fold, respectively; both P<۰.۰۱ vs. the control). However, Ang II-induced elevation of ۳H-TdR incorporation, and PKC activity was significantly inhibited by various doses of ADM and PAMP (all P<۰.۰۱ 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.