Adenosine A1 and A2A receptor cross-talk during ageing in the rat myocardium

Adenosine (Ado), a naturally occurring autacoid, exerts cardioprotective effects against myocardial ischemia and reperfusion injury. through activation of its receptors type 1 (A(1)) and 2A (A(2A)). Since ageing involves a complex change in these effects, we evaluated A(1) and A(2A) gene expression in left (LV) and right ventricle (RV) from 2-, 5-, 12-, and 21-month-old Sprague-Dawley rats. LV end-diastolic (EDD) and end-systolic (ESD) internal dimensions (mm) and LV fractional shortening (FS, %) were measured by M-mode echocardiography. Senescence was associated with a reduction in FS (42 +/- 1, 38 +/- 2, 39 +/- 2 and 35 +/- 2, in 2-, 5-, 12- and 21-month-old rats; p<0.02) and increases in EDD (7.5 +/- 0.2, 8.1 +/- 0.2, 8.5 +/- 0.2 and 8.8 +/- 0.2; p<0.001) and ESD (4.2 +/- 0.1, 4.4 +/- 0.2, 4.7 +/- 0.2 and 5.1 +/- 0.2; p=0.002). Ado A(1) mRNA levels were highest in 12 and 21-month-old animals in both ventricles (LV: p<0.001; RV: p=0.001). By contrast, Ado A(2A) gene expression was lower in the aged LV (p<0.001), but higher in the aged RV (p<0.001). These modifications of Ado receptor gene expression and especially the increase in A(1) receptor mRNA may partially explain the stronger antiadrenergic effects of Ado in the senescent heart. (C) 2003 Elsevier Inc. All rights reserved.