The Effect Of Neuropeptides Changes Of Myocardial And Renal Tissues On Cardiac Function In Chronic Renal Ischemia Of Rats Caused By Abdominal Aortic Banding

Research background:There is a high prevalence of RAS in middle-aged patients.The patients with RAS have an accelerated course of cardiovascular diseases and are more liable to accompany with heart failure.The mechanism of this phenomenon now attributed to the aberrant regulation of vasoactive substances in the body.Objective:Endothelin,the most potent endogenous vasoconstrictor,is activated in patients with RAS and may impair cardiovascular system through several mechanisms.CGRP and NO act as endogenous antagonists of ET-1.It is not clear whether CGRP and NO elevated with the course of development of RAS. The unproportionate relation between ET-1 and CGRP or NO may be the cause of heart failure followed by RAS.The function of CGRP synthesis at spinal dorsal root ganglions may be inhibited by chronic pathological damage of RAS. The consequent decreased level of CGRP in heart and kidney result in enhanced pathological effect of ET-1.This hypothesis has not been proved at present.In addition,sodium ferulic could act as ET receptor antagonist,but the therapeutic effect of it in RAS is not clear.Methods:Male wistar rats(weight 180-200g)were anesthetized with su mian xin.A midline incision was made in the abdominal cavity and a ligation of abdominal aorta between fight and left renal artery was made by silk suture.The narrow degree of aorta was about 50%which was controlled by ligated with a syringe needle(7#).The aorta was not ligated in sham operation group.After 8 weeks and 16 weeks of operation,invasive measurement of blood pressure and heart function were performed,and plasma level of ET-1,CGRP and NO were tested.At 16 weeks after operation,the rat were divided into 3 groups,sham operation group(SO),operation/untreated group(OP-U)and operation/treated (OP-T)group.SO and OP-U group were given intraperitoneal injection of normal saline,and OP-T group were given intraperitoneal injection of sodium ferulic(40mg/kg).After two weeks drug therapy,blood pressure,heart function and tissue content of ET-1,CGRP and NO were tested.CGRP mRNA of heart, kidney and dorsal ganglion were detected by RT-PCR.Results:Compared with sham operation group,the blood pressures of rats in operation group were elevated significantly,with decreased cardiac systolic and diastolic function,increased left ventricular mass index,and decreased weight of kidney at ischemic side.After 8 weeks plasma concentration of ET-1,CGRP rose slightly and concentration of NO decreased(p＞0.05)in operation group. After 16 weeks plasma concentration of ET-1 elevated significantly(96.3±11.6 vs.120.1±13.2 pg/ml,p＜0.05),CGRP and NO decreased(p＞0.05).There were no correlations between plasma ET-1,CGRP,NO and blood pressure. Plasma concentration of NO and the ratio of ET-1/CGRP had positive correlation with LV systolic function(r=0.73,p=0.01 and r=0.65,p=0.04, respectively).After 18 weeks,compared with SO group,the content of ET-1 in cardiac tissue were elevated significantly in OP-U group(361.0±118.7 vs. 571.9±148.2 pg/ml,p＜0.01),with decreased content of CGRP(74.4±24.8 vs. 40.9±17.4 pg/ml,p＜0.05)and NO(p＞0.05).Compared with OP-U group,the content of ET-1 in cardiac tissue were decreased significantly in OP-T group (571.9±148.2 vs.434.8±159.9 pg/ml,p＜0.05)with improvement of cardiac diastolic function(p＜0.05).There were negative correlation between the content of ET-1 in cardiac tissue and LV systolic/diastolic function(r=-0.37, p=0.038 and r=-0.41,p=0.02,respectively),and positive correlation between the content of CGRP in cardiac tissue and LV diastolic function(r=0.41,p=0.02). Changes of content of CGRP mRNA in heart and kidney were consistent with changes of content of CGRP in tissue.The expression of CGRP mRNA in dorsal root ganglion were increased in both OP-U and OP-T group as compared with SO group,especially significant in OP-T group(p＜0.05).Conclusions:In the state of chronic kidney ischemia caused by abdominal aorta ligation,content of ET-1 in cardiac tissue were increased with CGRP and NO decreased.The changes of these vasoactive substances impaired LV systolic and diastolic function.Sodium ferulic improved LV diastolic function by lowing content of ET-1 in cardiac tissue.The expressions of CGRP mRNA in dorsal root ganglion were increased during chronic kidney ischemia,but may play a second role in changes of content of CGRP in tissues.