Effects And Mechanism Of Soy Peptides On Cardiovascular System In Rat

In recent years, peptides from partial enzymatic hydrolysates of foodproteins have received greater attention from food scientists than ever before.Many biological peptides, with health benefits such as opioid activity,antihypertensive activity, antibacterial activity, mineral-binding activity,enhancement of intestinal activity, etc. have been classified and identified fromfood proteins hydrolysates. These peptides are inactive within the sequence ofthe parent protein but can be released during enzymatic digestion or foodprocessing. There exists a potential market for food industries, since it isgenerally accepted that many of the common diseases of prosperous nations(such as cancer, coronary heart disease,osteoporosis) are diet related and couldbe avoided with significant modification to our diets. Interest has focused on theisolation and identification of purified soy peptides from soy bean hydrolysatesafter enzymatic digestion. However, from the point of view ofcommercialization, it should be noted that it is the mixture of peptides, not asingle purified peptide, which would be applied as a health-enhancing ingredientfor use in "physiological functional foods". Soy peptides play significant rolesin cardiovascular system, but direct cardiovascular system effects remain to beelucidated.Therefore, the objectives of this work are: (1) to demonstrate the effects ofsoy peptides on hemodynamics and serum AngⅠand Ⅱ in vivo in normal andhypertensive rat;(2) examine the effects of soy peptides on rat thoracic aortarings and the underlying mechanism;(3) investigate the effects of soy peptideson hemodynamics in isolated working rat heart. (4) characterize soy peptides onthe action potential (AP), the Na + current (INa), L-type Ca2+ current (ICa-L) andtransient outword potassium current(Ito) in isolated cardiomyocytes.1. Effects of soy peptides on hemodynamics and serum AngⅠand Ⅱ invivo in normal and hypertensive ratIt is reported that soy protein food could decrease cariovascular events andsoy peptides could inhibit ACE in vitro. Soy protein was absorbed after beingdigested into oligo peptides, so we hypothesized that soy peptides was benefit tocariovascular system and depressing blood presure. ACE convert AngⅠto AngⅡ. In order to demonstrate if soy peptides could influence cardiovascularsystem and inhibit the activety of ACE, we examined soy peptides onhemodynamics and serum AngⅠand Ⅱ in vivo in normal and renalhypertensive rat.Results:Soy peptides could depress hemodynamics and serum AngⅡlevel inhypertensive and normal Wistar rat. But there has no significant difference innormal Wistar rat. Soy peptides could slightly increase serum AngⅠlevel inhypertensive and normal Wistar rat. But there has no significant difference.Conclusion:Soy peptides could depress blood pressure of renal hypertensive rat throughelevating serum AngⅡlevel. Soy peptides are safe to normal rat.2. Effects of soy peptides on rat thoracic aorta ringsSoy peptides could depress blood pressure of renal hypertensive rat andhave benificial properties to cardiovascular system. The vascular effects of soypeptides may play a more important role in these results. Blood pressure isrelated to many factors, such as nerve and tissue fluid. If soy peptides havedirect effects on aorta is to be elucidated. The aim of the present study is toinvestigate the effects of soy peptides on the tension of rat aorta rings.Results:Soy peptides could cause vasodilatation in rat aorta rings that wasprecontracted with phenylephrine and KCl in rat aorta rings with or withoutendothelium. And there has significat difference between the endothelium–intact rings and endothelium –destroyed rings.Conclusion:Soy peptides could cause vasodilatation in rat aorta rings and the functionalfactors that produced by endothelium may be take an important part in it.3. Effects of soy peptides on hemodynamics in isolated working rat heartsWe used Langendorff perfusion method to investigate the effects of soypeptides on aortic pressure (AP), left ventricular systolic pressure (LVSP), leftventricular end diastolic pressure (LVEDP), maximum rate of rise inintraventricular pressure during contraction(+dp/dtmax), maximum rate ofdecrease in intraventricular pressure during relaxation(-dp/dtmax), aortic flow(AF) and coronary flow (CF) in the isolated working rat hearts pretreated withisoprenaline and naloxone to investigate the effects of soy peptides onhemodynamics in hypertensive and normal Wistar rat.Results:Soy peptides decreased AP, LVSP, LVEDP and ±dp/dtmax in normal andisoprenaline preconditioned hearts. But have no influence on HR. These effectswere blocked by opioid receptor blocker: naloxone.Conclusions:In a conclusion, soy peptides have negative inotropic effects and couldattenuated the positive inotropic effects of isoprenaline in isolated working rathearts. The effects may be related to opioid receptor.4. Effects of soy peptides on action potential (AP) in isolated rat andguinea-pig ventricular myocytesThe function of heart is based on the electrical activity of the cardiacmyocytes. The electrical activity is characterized by action potential ofmyocytes. From action potential we can estimate the changes of different ioniccurrents of myocytes membrane. So we use patch-clamp technique to investigatethe effects of soy peptides on AP in isolated rat and guinea-pig ventricularmyocytes.Results:Soy peptides could attenuate the action potential duration (APD) inguinea-pig ventricular myocytes, increase resting potential in guinea-pig or ratventricular myocytes, but have no influence on amplitude of action potential(APA) of the two modles and have no influence on action potential duration(APD) in rat ventricular myocytes.Conclusion:Soy peptides have no influence on sodium current (INa), may be inhibitL-type Ca2+ current (ICaL), inward rectifier K+ current (Ik1) and transient outwordpotassium current(Ito).5. Effects of soy peptides on the sodium current (INa) in isolated ratventricular myocytesIn order to validate the result that soy peptides have no influence on INa, weused patch clamp technique to investigate the effects of soy peptides on thesodium Na + current (INa) in isolated rat ventricular myocytes.Results:There has no change of INa in isolated rat ventricular myocytes before andafter giving soy peptides.Conclusion:Soy peptides could not influence INa in isolated rat ventricular myocytes. Itis consistent with our hypothesis.6. Effects of soy peptides on L-type Ca2+ current (ICaL) in isolated ratventricular myocytesCardiac EC coupling is initiated by Ca2+ influx into cardiac myocytes viavoltage-dependent L-type Ca2+ channels. Soy peptides have negative inotropiceffects in isolated working rat heart. Soy protein provided satiety signals throughopioid receptors. Recently, κ(kappa)andδ(delata)opioid receptor transcriptswere detected in stomach, small intestine, large intestine and heart. Soy proteinand milk protein hydrolysates could take effect through OPRs of gastrointestinal,it may be interact with OPRs of heart. It was reported that opioid receptorsregulate the L-type calcium channel in submandibular ganglion neurons . Anddown regulation of ICa-L may attribute to the shorting of APD. Thus, wehypothesized that there may be an interaction between soy peptides, ICa-L andOPRs in heart.Therefore, the purpose of the present study was to determine whether soypeptides had effects on ICa-L and whether soy peptides had relation to OPRs inadult rat ventricular myocytes.Results:Soy peptides depressed ICa-L in a dose-dependent manner. Pretreatment withopioid receptors (OPRs) antagonist naloxone abolished the inhibitory effect ofsoy peptides on ICa-L.Conclusion:Soy peptides depressed ICa-L in adult rat ventricular myocytes and theeffects havd relation with cardiac OPRs.7. Effects of soy peptides on transient outword potassium current(Ito) inisolated rat ventricular myocytesThere are different ion channls in rat and guinea-pig ventricular myocytes.For example, we can record Ito in rat myocytes and Ik in guinea-pig myocytes,but can not record Ik in rat myocytes and Ito in guinea-pig myocytes. This is thebasis of different AP shap between rat and guinea-pig. Soy peptides depressedICa-L in adult rat ventricular myocytes and attribute to the shortening of APD. Itis consistent with the result obtained from guinea-pig APD shortening. But soypeptides have no influence on rat APD. Inhibition of Ito may cause prolongationof APD. If soy peptides may depresse Ito is to be tested. So we investigate theeffects of soy peptides on transient outword potassium current(Ito) in isolated ratventricular myocytes.Results:Amplitude of Ito was depressed and the I-V curve came down after beinggiven soy peptides in rat isolated ventricular myocytes.Conclusion:Soy peptides depressed Ito in rat ventricular myocytes.All these results indicate that soy peptides could depress blood pressure ofrenal hypertensive rat and have negative inotropic effects in isolated working rathearts.The relaxation effects in rat aorta artery and reduction of serum AngⅡmay contribute to blood depression. And the vascular endothelial cells are likelyinvolved in the aorta artery relaxation. Whereas inhibition of voltage-dependentCa2+ channel and receptor-operate Ca2+ channel contribute in part to theendothelium-independent relaxation. The negative inotropic of soy peptides inisolated working rat hearts maybe related with opioid receptors and ICa-L. Thealleviation of ICa-L and Ito are benefit to the cardiovascular system . The safety ofsoy peptides on normal rat and the benefit to cardiovascular system give soypeptides a bright prospective future.