| BACKGROUND:Cardiovascular diseases is one of the most dangerous diseases which damages people heath in these days. In recent years, more and more attentions have been paid to cardiovascular active factors such as ET-1, AngⅡ, ADM, etc. These factors play a very important role in the pathologic and physiologic process of cardiovascular diseases. Therefore it is necessary to find out the role of every factor in cardiovascular diseases and their relations between each other. Urotensin II (UII) is a peptide that was originally separated from fish. It is verified that UII has a wide distribution in nervous system of both mollusc and mammals. Ames et al found that UII and its special receptor, an isolate G-protein coupled receptor 14, which was homologous with the rat's GPR14, had a wide distribution in cardiovascular system. Binding its receptor, urotensin can elicit the increase of [Ca~2+] in cell, and participate in a series of cardiovascular response such as vascular contraction and cardiac function inhibition. Urotensin-Ⅱ, the most potent mammalian vasoconstrictor identified, whose effect is nearly twenty times stronger than ET-1 can stimulate the proliferation of vessel smooth muscle cells and cardiac fibroblasts. Terefore, UIIbecomes a hotspot in cardiovascular field. While ADM, which was first found by Kitamural in pheochromocytoma in 1993, is an active peptide with strong function of vasodilating, diuresis, stepping down blood pressure and inhibiting vascular smooth muscle cells. Recently, a closed relationship between UII and ET-1 as well as other vascular active factors was found, they participate in compensatory regulation in cardiovascular diseases. But there are few studies on the relationship between ADM and UII, whether the relationship is antagonistic or synergistic is uncertain. As shown in some studies, the decreased UII and the increased ADM were parallel with the severity of CHF, and ADM inhibited the proliferation of VSMC which is induced by UII through inhibiting MAPK activation. In this research, the effect of UII on the secretion of ADM in culttivated HVEC is observed dynamicly, and the possible mechanism of signal transduction is studied by observing the change of ADM secretion after different signal transduction pathway has been obstructed, which can help study the interaction of UII and ADM in cardiovascular disease pathogenesis. It may provide theory basis and objective guideline for diagnosis and treatment of cardiovascular diseases. OBJECTIVE:To study the effect of UII on ADM secretion in HVEC and its possible mechanism. METHODS:1. The quantity of ADM secreted by HVEC was measured by RIA in different groups which was cultured with varied concentration (10"7? 10"8> 10"^ 10"10mol/L) of UII;2. The quantity of ADM secreted by HVEC was measured by RIA in different times after cultured with UII(10"7 mol/L);3. Varied signal transducting retarder, ERKs inhibitor PD98059, calcimodulinantagonist W7, P38-MAPK inhibitor SB202190, nicardipine, PKC inhibitor H7 and Calcineurin antagonist CsA was used to investigated its effect on ADM secretion by UII induced. RESULTS:1. UII increased the secretion of ADM in HVEC in a dose-dependent manner. The quantity of ADM secreted by HVEC significantly increased in corporation with varied concentrations of UII(10~10-10"7mol/L) as compared with control (36.07 + 8.96, 42.88 + 4.75, 46.11 ±8.54, 58.19±8.54 pg/L vs 22.63 ±2.98pg/L,P<0.01).2.UII increased the secretion of ADM in HVEC in a time-dependent manner. The quantity of ADM secreted by HVEC significantly increased after cultured with UII (10"7mol/L) for 6, 12 and 24h as compared with control (35.35 + 2.96, 43.96+ 4.12, 63.42 + 8.78 pg/L vs 19.53 ±0.88, 23.92±2.43, 37.58±4.94pg/L, P<0.0\).3. PD98059, W7, SB202190 and nicardipine inhibited the effect of UII in inducing secretion of ADM with the rate of 67%(P<0.01), 77%(P<0.01), 23%(JP<0.05), 24%(P<0.05), respectively; No changes were observed in H7 and CsA group (P>0.05). CONCLUSION:1 .Our results suggested that UII, as a vasoconstrictor, may induce secretion of ADM in HVEC in a time-dependent and dose-dependent manner.2.This effect was possibly conducted by ERKs, CaM, P38-MAPK and Ca2+ signal transduction pathway.
|
PDF Full Text Request