Age-related changes of bradykinin B1 and B2 receptors in rat heart
Age-related changes of bradykinin B1 and B2 receptors in rat heart
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DOI：
10.1152/ajpheart.01287.2004
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发表时间：
2005-07-01
影响因子：
4.8
通讯作者：
Gavras, H
中科院分区：
文献类型：
--
作者：
Kintsurashvili, E;Duka, A;Gavras, H
衰老是血管疾病发展的主要危险因素，如高血压和动脉粥样硬化，导致终末器官损伤，特别是心力衰竭。已证明缓激肽通过影响心肌缺血条件下的代谢过程和组织灌注而具有心脏保护作用。其作用通过缓激肽B-1-和B-2-型受体（B（1）Rs和B（2）Rs）发挥，但对这些受体在衰老过程中的功能状态知之甚少。本研究旨在探讨大鼠心脏B1 R和B2 R基因及蛋白表达的变化是否与心脏结构和功能的增龄性改变有关。使用实时PCR，我们发现，与年轻大鼠（3月龄）相比，老年大鼠（24月龄）心脏中B1 R mRNA表达增加了2.9倍，而B2 R基因表达保持不变。蛋白质印迹分析表明，在蛋白质水平上的表达B2 R在年轻大鼠中比老年大鼠高约两倍，而B1 R蛋白在老年大鼠中比年轻大鼠高约两倍。本研究结果为心脏缓激肽B（1）Rs和B（2）Rs的增龄性变化提供了明确的功能和分子证据。由于缓激肽的心脏保护作用是通过B（2）Rs生理介导的，而B（1）Rs是由组织损伤诱导的，因此这些结果表明，与年龄相关的B2 R蛋白水平降低可能使心脏易受缺血性损伤，而B1 R表达和活性增加可能代表衰老心脏的代偿反应。
Aging is a major risk factor for the development of vascular diseases, such as hypertension and atherosclerosis, that leads to end organ damage and especially heart failure. Bradykinin has been demonstrated to have a cardioprotective role by affecting metabolic processes and tissue perfusion under conditions of myocardial ischemia. Its actions are exerted via the bradykinin B-1- and B-2-type receptors (B(1)Rs and B(2)Rs), but the functional status of these receptors during the aging process is poorly understood. This study aims to investigate whether changes in B1R and B2R gene and protein expression in rat heart are associated with the age-related alterations of cardiac structure and function. Using real-time PCR, we found that B1R mRNA expression increased 2.9-fold in hearts of older rats (24 mo of age) compared with younger rats (3 mo of age), whereas B2R gene expression remained unchanged. Western blot analysis showed that expression of B2R at the protein level is approximately twofold higher in young rats compared with old rats, whereas the B1R protein is approximately twofold higher in old rats compared with young rats. The present results provide clear functional and molecular evidence that indicate age-related changes of bradykinin B(1)Rs and B(2)Rs in heart. Because the cardioprotective actions of bradykinin are physiologically mediated via the B(2)Rs, whereas the B(1)Rs become induced by tissue damage, these results suggest that age-related decreases in B2R protein levels may leave the heart vulnerable to ischemic damage, and increases in B1R expression and activity may represent a compensatory reaction in aging hearts.