Abstract

AM and PAMP, processed from the same precursor of preproAM, have differential biological properties: AM dilates blood vessels and presumably affects the vascular remodeling, while PAMP inhibits catecholamine secretion from sympathetic nerve ending. Ald has been reported to be involved in the cardiovascular remodeling. Thus, the aim of this study is to examine the effects of Ald on AM and PAMP production and preproAM gene expression in human VSMCs. Cultured human aortic VSMCs were incubated with various concentrations of Ald. PreproAM gene expression was measured by real-time quantitative polymerase chain reaction(Hypertension 2000; 35: 1210), and AM and PAMP concentrations in the conditioned media were determined by specific radioimmunoassays. Cultured human VSMCs time-dependently secreted both AM and PAMP into the media, while the secretion rate of AM was much higher than that of PAMP (AM,13.6±0.3; PAMP, 2.2±0.1 fmol/105cells/48 h; p<0.01). Ald increased preproAM mRNA expression and AM secretion of VSMCs in a dose- and time-dependent fashion. After the incubation with 10-6mol/L Ald for 48 h, preproAM mRNA/GAPDH mRNA and AM secretion significantly (p<0.01) increased to the levels of 292% and 232% of controls, respectively. HPLC analyses showed that secreted AM was identical to hAM(1-52)-NH3 in the untreated and Ald-stimulated cells. Although the increase in preproAM mRNA resulted in the parallel increase of AM secretion, PAMP secretion remained unchanged at any concentration of Ald. When added exogenously, 10-6mol/L synthetic AM disappeared more rapidly than PAMP(T1/2: AM, 3.4±0.4h; PAMP, 9.4±1.6h; p<0.01), indicating that a clearance rate of PAMP by VSMCs is lower than that of AM. These results suggest a possible autocrine or paracrine role of AM in modulating the vascular tone or Ald-induced remodeling, meanwhile the processing or metabolism of PAMP differs from that of AM, in human VSMCs.

This content is only available as a PDF.
You do not currently have access to this article.