Aging Effect Of Insulin Sensitivity In Rat Aorta And Its Principal Mechanism

With the aged-society and less exercises,cardiovascular diseases and diabetesbecome more and more common,while cardiovascular system dysfunctionbecause of aging was paid more attention.It was found recently that,besidesmetabolism regulation effects, insulin also has important effects on cardiovascularsystem.Insulin resistance links cardiovascular diseases with metabolize disorder as"common soil",insulin sensitivity decline is a danger factor to cardiovasculardisease.So make clear the change of insulin sensitivity when aging and themechanism under it is senseful for preventing and curing insulin resistance,protectcardiovascular system against aging.However,the reseach about insulin sensitivityis always done in liver,muscle and adiposeness,decline of insulin sensitivitybecause of aging in vascular system is under exploration,the relationship betweeninsulin sensitivity and eNOS-NO system in vascular hasn't explicit evidence.The aim of this study is to survey the aging effect of insulin sensitivity in rataorta,investigate the principal mechanism.Experimental animals were 20 aged SD rat (18 months old) and 20 adult SD rat (15 weeks old) in contrast.Theexperiments are consisted of two parts:1.The effect of cumulative application ofinsulin on the norepinephrine-induced contraction in isolated aortic rings fromboth adult and aged .2. Investigate the principal mechanism of the vasodilatationevoked by insulin.The main results are as follows:1. The vasodilatation effect of insulin on rat aortaPrepare rat aorta rings width 3 mm,precontracted it with 1×10-6 mol/L NE,dipinto insulin after steady,make sure its accumulating concentration reach to 50,100,150,200,250 U/L .It's observed that insulin can dose-dependent(50 to 250U/L)relax adult rat aorta which was contracted by NE,the maximal relaxation is38.1%±2.0%(n=6).This relax effect is endothelium-dependent,for after theremoval of the aortic vascular endothelium,the vasodilatation evoked by insulin isdecrease obviously(14.3%±2.4%, P<0.05, n=6).With the presence of the NOsynthase inhibitor-L-NAME,the vasodilatation effect also decreasedobviously(15.5%±2.8%, P<0.05, n=6). L-NAME alone can not affect tension ofvessel.2.The aging change of insulin vasodilatation on aortaIn aged aortic rings,the maximal vasodilatation evoked by insulin is20.0%±2.7% (n=6).Compared with adult, the vasodilatation effect decreasedobviously(20.0±2. 7 vs 38.1±2.0%,P<0.05, n=6).So insulin sensitivity of agedrat aorta declines,endothelium function is disordered.3.The relationship of eNOS-NO system with insulin sensitivityTo explore the mechanism of insulin sensitivity decline in aged rat aorta,we measured its eNOS-NO system express and bioactivity.It's proved that thetissue concentration of NO is decreased(0.6±0.8 vs 1.0±0.9 umol/gprot, P<0.05),the bioactivety of eNOS also decreased(2.3±0.1 vs 18.1±1.2 U/mgprot,P<0.05).Assess the expression of eNOS protein in aorta, immunostaining photoesshow in aged aorta,eNOS protein content decrease while western blot also showthe expression of eNOS phospholinase protein decrease ( P<0.05,n=6).In conclusion,our data demonstrate that:1 Insulin can dose-dependent relax adult rat aorta.2 The vasodilation effect evoked by insulin decresed obviously in aged aortawhen compared to adult, insulin sensietivity of vessel declined.3 This vasodilation effect of insulin is related to endothelium-deprived NO.4 In aged rat aorta, endothelium-derived NO release less,both of itsendothelium eNOS protain expression and bioactivity are decreased, lead toeNOS-NO system decline,it may be the main reason for decline of insulinsensitivity on aorta.