Effects of β-blockers on vascular aging in spontaneously hypertensive rats
Aim To explore the preventive effect and potential mechanism of β-blockers in vascular aging of spontaneously hypertensive rat(SHR).Methods 24 three-month-old male spontaneously hypertensive rats were ran-domly divided into placebo group,nifedipine group,nifedipine+metoprolol group and metoprolol group,treated with edible starch,60 mg nifedipine sustained-release tablets,40 mg nifedipine sustained-release tablets+75 mg metoprolol sustained-release tablets and 150 mg metoprolol sustained-release tablets,respectively.The rats fed with common diets for 9 months,and the blood pressure,heart rate and other general condition of the rats were dynamically measured.HE stai-ning was used to observe the morphological characteristics of femoral aorta in rats.The vasomotor function of isolated fem-oral artery was tested by circumferential perfusion,immunofluorescence histological staining and real-time polymerase chain reaction(RT-PCR)were used to determine the expression of aging related genes p53 and p21,as well as endoplasmic re-ticulum stress related genes CHOP and XBP1.Results Compared with placebo group,systolic blood pressure de-creased by about 30％,diastolic blood pressure decreased by about 20％,and heart rate decreased by 9％,36％and 41％(all P＜0.01)in nifedipine group,nifedipine+metoprolol group and metoprolol group,respectively.Compared with pla-cebo group,the systolic and diastolic functions of nifedipine group,nifedipine+metoprolol group and metoprolol group were significantly improved and the intima-media thickness decreased by 24％,14％and 37％(all P＜0.01),respec-tively.Compared with nifedipine group and nifedipine+metoprolol group,the systolic and diastolic functions of metopro-lol group were significantly improved and the intima-media thickness decreased by 18％and 27％(all P＜0.01),re-spectively.Compared with the placebo group,the expression levels of p53 protein,p53 mRNA,p21 protein,p21 mR-NA,CHOP protein,CHOP mRNA,XBP1 protein and XBP1 mRNA in nifedipine group decreased by 35％(P＜0.01),23％(P＜0.05),25％(P＜0.01),3％(P＞0.05),51％(P＜0.01),24％(P＞0.05),21％(P＜0.01)and 23％(P＞0.05),the nifedipine+metoprolol group decreased by 36％(P＜0.01),42％(P＜0.01),4％(P＞0.05),24％(P＜0.05),32％(P＜0.01),44％(P＜0.05),13％(P＜0.01)and 42％(P＜0.05),the metoprolol group de-creased by 47％(P＜0.01),43％(P＜0.01),42％(P＜0.01),49％(P＜0.01),78％(P＜0.01),56％(P＜0.01),32％(P＜0.01)and 81％(P＜0.01).Compared with nifedipine group and nifedipine+metoprolol group,metoprolol group further inhibited the expression of genes related to aging and endoplasmic reticulum stress.Conclu-sions The arteries of spontaneously hypertensive rats show significant aging.β-blockers are better than calcium chan-nel blockers in inhibiting vascular aging of spontaneously hypertensive rats,and at high doses β-blockers improve the de-gree of vascular aging better than combination therapy,and their mechanism may be related to the inhibition of endoplas-mic reticulum stress.
万方数据
维普
