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

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

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.

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.