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<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.