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 (A1) and 2A (A2A). Since ageing involves a complex change in these effects, we evaluated A1 and A2A 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 A1 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 A2A 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 A1 receptor mRNA may partially explain the stronger antiadrenergic effects of Ado in the senescent heart.
Arosio
Beatrice
B
Department of Internal Medicine and Gerontology, Ospedale Maggiore IRCCS, Cattedra di Geron. e Geriatria, Via Pace 9, 20122 Milan, Italy.
Perlini
Stefano
S
Calabresi
Carmen
C
Tozzi
Rossana
R
Palladini
Giuseppina
G
Ferrari
Alberto U
AU
Vergani
Carlo
C
Annoni
Giorgio
G
D000375:Aging / Q000502:physiology*; D000818:Animals; D004452:Echocardiography; D015870:Gene Expression; D006352:Heart Ventricles; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020239:Receptor Cross-Talk / Q000502:physiology*; D043682:Receptor, Adenosine A1 / Q000235:genetics*; D043705:Receptor, Adenosine A2A / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A