Long-Term Stimulation of Adenosine A2b Receptors Begun After Myocardial Infarction Prevents Cardiac Remodeling in Rats

Abstract

Background-Adenosine inhibits proliferation of cardiac fibroblasts and hypertrophy of cardiomyocytes, both of which may play crucial roles in cardiac remodeling. In the present study, we investigated whether chronic stimulation of adenosine receptors begun after myocardial infarction (MI) prevents cardiac remodeling. Methods and Results-MI was produced in Wistar rats by permanent ligation of the left anterior descending coronary artery. One week after the onset of MI, animals were randomized into 8 groups: vehicle, dipyridamole (DIP; the adenosine uptake inhibitor, 50 mg/kg), 2-chroloadenosine (CADO; the stable analogue of adenosine, 2 mg/kg), and CADO in the presence of the nonselective adenosine receptor antagonist 8-sulfophenyltheophylline (8-SPT) or the selective antagonist for adenosine A1, A2a, A2b, or A3 receptor. Three weeks after treatment, hemodynamic and echocardiographic parameters in the DIP and CADO groups were significantly improved compared with the vehicle group. These hemodynamic and echocardiographic improvements were blunted by either 8-SPT or the selective adenosine A2b antagonist MRS1754 but not by the selective antagonists for other subtypes of adenosine receptors. The collagen volume fraction was smaller, and gene expression of the molecules associated with cardiac remodeling such as matrix metalloproteinase in noninfarcted areas was reduced in the DIP and CADO groups compared with the vehicle group, both of which were attenuated by either 8-SPT or MRS1754. Conclusions-Long-term

Adenosine in fibrosis

“…Adenosine A 2B receptor stimulation has been shown to suppress collagen production by cardiac fibro-blasts, suggesting a protective effect of this receptor in myocardial fibrosis [92]. These results are consistent with the observation that A 2B receptor stimulation prevents cardiac remodeling and protects against elevations in cardiac collagen volume and cardiac fibrosis following induction of myocardial infarction by ligation of left anterior descending coronary artery in Wistar rats, with subsequent improvement in cardiac function [93]. …”

Cardiac purinergic signalling in health and disease

“…However, long-term stimulation of A2BR commenced after MI prevented cardiac remodelling in rats [632] and contributed to post-infarction heart failure [633]. In a more recent study, it was found that the selective blockade of A2BR reduced cardiac remodelling following acute MI in mice [634].…”

Exogenous ARC down-regulates caspase-3 expression and inhibits apoptosis of broiler chicken cardiomyocytes exposed to hydrogen peroxide

“…Cardiomyocytes are terminally differentiated cells. The loss of cardiomyocytes is not compensated by efficient cell proliferation (Wakeno et al, 2006). Therefore, determining how to prevent cardiomyocyte apoptosis could be an effective strategy to lower heart damage by reactive oxygen species.…”

“…Our previous studies have shown that endogenous reactive oxygen species can induce cardiomyocyte apoptosis in ascitic broiler chickens. Because cardiomyocytes are terminally differentiated cells, the loss of myocardial cells cannot be compensated by efficient cell proliferation (Wakeno et al, 2006). Cardiomyocyte apoptosis could therefore be responsible for heart failure induced by a reduced number of myocardial cells in ascitic broiler chickens.…”