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1 Hypertension and Atheroscierosis Section of the Department of Medicine, Boston University School of Meidicne, Boston, MA, USA
* To whom correspondence should be addressed. E-mail: hgavras{at}bu.edu.
Aging is a major risk factor for the development of vascular diseases such as hypertension and atherosclerosis, leading to end organ damage, 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 B1 and B2 type receptors (B1R and B2R) 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 the heart of older rats (24 months old) compared to younger rats (3 month old), whereas B2R gene expression remained unchanged. Western blot analysis showed that expression of B2R at the protein level is ~2 fold higher in young rats compared to old rats, whereas the B1R protein is ~2 fold higher in aged rats compared to young rats. The current results provide clear functional and molecular evidence indicating age-related changes of bradykinin B1R and B2R in the heart. Since the cardioprotective actions of bradykinin are physiologically mediated via the B2R, whereas the B1R becomes induced by tissue damage, these results suggest that age-related decrease in B2R protein levels may leave the heart vulnerable to ischemic damage and increase in B1R expression and activity may represent a compensatory reaction in the aging heart.
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