Cardiovascular and renal effects of 5-aminoimidazole-4-carboxyribonucleoside (AICAR) in the deoxycorticosterone acetate (DOCA)-salt rat model of hypertension.

Previous studies suggest that exercise training mitigates blood pressure in hypertensive animal models. While exercise training may be an effective therapeutic for hypertension treatment and prevention, many patients diagnosed with hypertension can be noncompliant with lifestyle modifications that involve physical activity or are unable to participate in strenuous activity due to the severity of their hypertension. AMP-activated protein kinase (AMPK) is responsive during metabolic stressors, plays a vasoprotective role in endothelial function, and is stimulated during exercise training. Studies have suggested that signaling pathways activated by AMPK may play a protective role in hypertensive models given AMPK's involvement in redox balancing. The purpose of this study is to determine the therapeutic potential of AICAR (5-aminoimidazole-4-carboxamide-3-ribonucleoside), a potent AMPK stimulator, for ameliorating hypertension. Uninephrectomized Sprague Dawley rats received DOCA-salt treatment and daily administration of either AICAR (100 mg/kg/day) or vehicle (20 % DMSO) subcutaneously for 21 days. Cardiovascular and renal function were assessed by radiotelemetry, tail cuff, proteinuria, and GFR. No differences in final MAP were detected in AICAR and vehicle treated DOCA-salt groups, respectively (183.6 ± 26.2 and 179.4 ± 26.5 mmHg). Notably, no changes in renal injury or function were detected with AICAR treatment as shown by the final GFR and proteinuria. From these findings we concluded that exogenous administration of AICAR does not attenuate hypertension in the DOCA-salt model despite increased AMPK activation.