| PrefaceEndothelial cells play an important local regulatory role by secreting substances that control vascular tone, including NO, which is derived from the metabolism of L - arginine by NO synthase, a constitutive enzyme that is present in endothelial cells. Aging is characterized by the presence of endothelial dysfunction. There is reason to believe that the renin angiotensin system (RAS) could be activated in aging, particularly at the local, vascular level. Angiotensin II is the important substance that RAS is activated. Angiotensin II promotes endothelial dysfunction through angiotensin - 1 ( AT1 ) receptor - mediated generation of the superoxide anions from smooth muscle and endothelial cell membrane - bound reduced nicotinamide adenine dinucleotide - dependent oxidase. We hypothesized that the RAS contributes to endothelial injury and that angiotensin II inhibition with AT1 receptor blockade will reverse and improve age - related endothelial dysfunction. Experimental evidence indicates that Losartan, AT1 receptor antagonist , improves endothelial impairment in hypertension, atherosclerosis , diabetic and so on, but there are no reports about improving endothelial impairment with Losartan in aging, and no data are available concerning NO availability and the role of oxidative stress associatedwith it. Therefore, the aim of the study was to investigate whether Losartan improve age - related endothelial dysfunction in rats and assess whether Losartan increases NO availability. We hope this research may be helpful to provide preventive and therapeutic methods for clinical work.Materials and MethodsMaterials1. Animals: 30 male Wistar rats , 10 adult rat (3 -4 months), 20 old rats (20-22 months) were randomized to divided into 2 groups, one group (n = 10) was treated with Losartan ( 20mg. kg-1. d-1) for 8weeks, the other group served as control (n=10).2. Reagent: losaran, NE, Ach, SNP, iNOS test kits, eNOS test kits.3. Apparatus: R6000 polyphysiological system, 1599920-401 tissue organ bath system, AP - 621G amplitude balance controller, TP200P pressure transducers, XWT -204 balance recorder, PE -50 polyvinyl tube, DIAX900 electric tissue homogenizer, DU -640 spec-trophotometer.Methods1. Systemic artery pressure measurementAt the end of Sweeks after Losartan treated, the rats were anesthetized with phenobarbital sodium (60mg/kg). The left carotid arter-y was cannulated with a PE - 50 polyvinyl tube for the measurement of systemic artery pressure. The catheters were connected with pressure transducers (TP200P) and the systemic artery pressure was recorded with the polysiogical system.2. Isolated animal experimentAfter recording the systemic artery pressure, the aorta of Wistar rats were placed in cold (4 C) krebs and dissected out and cleaned of the surrounding tissues. Aortic rings were mounted between two stainless steer hooks for tension recording. The optimum contraction was 1.5g and tissues left to equilibrate in 20ml krebs'solution (for 1h at 37 C and bubbled with 95% O2+5% CO2). Following 60 min equilibration under these conditions, the response to 2+ 10-7 mol /L norep-inephrine was performed and cumulative concentration response curves of Ach(10-8-10-5mol/L) induced vasodilation were established. Followed by wash - out and further equilibration, cumulative concentration response curves of sodium nitroprusside (10-10- 10-6mol/L) induced vasodilation were also established.3. NO Production AssayNitrate reductase method was used. 10% tissue homogenate was prepared with thoracic aorta under low temperature, followed by cen-trifugalizing, obtaining supemate, adding various reagents to super-nate in turn, colorimetric determinating and calculating finally.4. NOS Activity AssayVarious reagents were put in 10% thoracic aorta homogenate according to kits' direction, colorimetric determination and calculation were followed.5. Statistical analysisResults were expressed as means standard deviation. Statistic a-nalysis were done using SPS...
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