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Age-related changes of bradykinin B₁ and B₂ receptors in rat heart

Hypertension and Atherosclerosis Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts

Submitted 21 December 2004 ; accepted in final form 4 February 2005

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 B₁- and B₂-type receptors (B₁Rs and B₂Rs), 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 B₁Rs and B₂Rs in heart. Because the cardioprotective actions of bradykinin are physiologically mediated via the B₂Rs, whereas the B₁Rs 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.

myocardium; gene expression; receptor protein levels; aging; cardioprotection

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