[OP.8C.05] A2A RECEPTOR-MEDIATED ACTIVATION OF REGULATORY T CELLS ATTENUATES HYPERTENSION-INDUCED CARDIORENAL CONSEQUENCE

    loading  Checking for direct PDF access through Ovid

Abstract

Objective:

Inflammatory processes plays a pivotal role in pathogenesis of hypertension. Previous study have indicated that A2A receptor is closely related with immunogenic anti-inflammation process. The present study aimed to elucidate whether the activation of A2A receptor is involved in the regulation of hypertension-induced cardiovascular consequence via regulating immunoresponse.

Design and method:

Deoxycorticosterone acetat (DOCA)-salt hypertensive mice were injected intraperitoneally with specific A2A receptor agonist (CGS21680) or antagonist (istradefylline) or PBS respectively. Fourteen days after DOCA-salt infusion, the expressional diversity of immune-related cytokines and chemokines were detected by quantitative real time PCR and western blot. Flow cytometric analysis was used to assess spleen CD4+, CD8+ and Foxp3+ T cells. The cardiovascular function of DOCA-salt mice was detected by wire myography and echocardiography.

Results:

The treatment of CGS21680 resulted in an dramatically increase of regulatory T cells (Tregs,CD4+Foxp3+) in spleen, accompanied by the increased volume and weight of spleen (Figure), while istradefylline accelerated DOCA-salt induced hypertension inflammation. CGS21680 stimulation also resulted in decreased inflammatory cytokins level as IL-6 and MCP1 in heart and renal. Relax function of aorta significantly elevated in CGS21680-treated DOCA-salt mice and the echocardiographic results display an obvious improvement of cardiovascular functions.

Conclusions:

These datas indicate that CGS21680 acts through A2A receptor to increase regulatory T cells, causing the attenuation of hypertension-induced cardiovascular injury. Overall, A2A receptor may be a novel role in hypertension therapeutic strategy.

Related Topics

    loading  Loading Related Articles