Effect of aging on myocardial adenosine production, adenosine uptake and adenosine kinase activity in rats.
Effect of aging on myocardial adenosine production, adenosine uptake and adenosine kinase activity in rats.
复制标题
衰老对大鼠心肌腺苷产生、腺苷摄取和腺苷激酶活性的影响。
DOI：
10.1006/jmcc.1998.0877
复制
发表时间：
1999
影响因子：
5
通讯作者：
DobsonJr,JG
中科院分区：
文献类型：
--
作者：
Lorbar,M;Fenton,RA;Duffy,AJ;Graybill,CA;DobsonJr,JG
老年心脏的间质液和冠状流出液中腺苷水平超过年轻成人心脏。本研究探讨了Fischer 344大鼠心脏中可能导致所观察到的差异的机制。(1)腺苷的总产量测定在离体灌流心脏通过测量冠状动脉流出液腺苷含量，同时抑制腺苷脱氨和再磷酸化与赤羟基壬基腺苷（EHNA）和碘杀结核菌素（ITC），分别。年轻（3-4个月）和老年（20-21个月）心脏的总腺苷产生量相似，分别为31.8±6.6和38.4±3.3 nmol/min/g干重。然而，与老年心脏相比，用β-肾上腺素能药物异丙肾上腺素刺激引起年轻心脏腺苷产生显著增加。(2)在离体灌注心脏中，通过测定14 C-腺苷灌注20分钟后心肌对14 C的摄取来评价腺苷转运。与年轻成人心脏相比，老年人无药物心脏的腺苷摄取减少了17%至25%。(3)腺苷转运特性测定与硝基苄基硫代肌苷饱和结合研究在心室膜制剂。老年心脏的Bmax值显著低于年轻成人心脏（老年和年轻心脏分别为140.2±1.5 fmol/mg和191.9±2.3 fmol/mg），表明老年心脏中转运蛋白位点数量减少。然而，Kd值随着年龄的增长而降低，表明老年人与年轻人心脏中腺苷转运蛋白的亲和力增加。(4)测定老年和青年心室肌匀浆中腺苷激酶的活性和动力学。两种活动之间无统计学差异。总之，这些结果表明，增加间质腺苷水平在老年心脏的结果减少摄取腺苷的心室心肌。
Adenosine levels present in the interstitial fluid and coronary effluent of the aged heart exceed those of the young adult heart. The present study investigated mechanisms in the Fischer 344 rat heart which may be responsible for the observed differences. (1) Total production of adenosine was determined in isolated perfused hearts by measuring coronary effluent adenosine content while inhibiting adenosine deamination and rephosphorylation with erythrohydroxy-nonyladenosine (EHNA) and iodotubercidin (ITC), respectively. Total adenosine production was similar in both young (3–4 month) and aged (20–21 month) hearts at 31.8±6.6 and 38.4±3.3 nmol/min/g dry wt, respectively. However, stimulation with theβ-adrenergic agent, isoproterenol, elicited a significantly greater increase in adenosine production in the young vs. aged heart. (2) Adenosine transport was evaluated in isolated perfused hearts by determining14C uptake by the myocardium after 20 min of14C-adenosine perfusion. Adenosine uptake in the agent-free heart was found to be decreased 17 to 25% in aged compared to young adult hearts. (3) Adenosine transport characteristics were determined with nitrobenzylthioinosine saturation-binding studies in ventricular membrane preparations. The Bmaxvalues were significantly lower in aged than young adult hearts (140.2±1.5 fmol/mg and 191.9±2.3 fmol/mg in aged and young hearts, respectively) indicating a decreased number of transporter sites in the aged heart. However, the values for Kdwere decreased with aging, suggesting an increase in the affinity of the transporter for adenosine in the aged vs. young adult heart. (4) The activities and kinetics of adenosine kinase were determined in homogenates of aged and young adult ventricular myocardium. No statistical difference was found between the two activities. Taken together these results suggest that increased interstitial adenosine levels in the aged heart result from decreased uptake of adenosine by the ventricular myocardium.