P598Deleterious effects of cardiac aldosterone and exercise in type 2 diabetic mice.

Cardiovascular Research

PubMedID: 25020321

Fazal L, Polidano E, Merval R, Coutance G, Delcayre C, Samuel J. P598Deleterious effects of cardiac aldosterone and exercise in type 2 diabetic mice. Cardiovasc Res. 2014;103 Suppl 1S108.
INTRODUCTION
Scarcity of microvessels and deregulation of the renin-angiotensin-aldosterone system contribute to the development of heart failure in diabetes. We showed that cardiac aldosteronism inhibits the onset of cardiomyopathy in type 1 diabetic mice by preventing capillary rarefaction (Messaoudi, 2009). Another promising therapeutic approach to prevent diabetic heart disease is exercise training (Ex). Exercise is beneficial in diabetic cardiomyopathy in human and experimentally. Thus, the objective of the study was to determine whether cardiac aldosterone-induced angiogenesis in type 2 diabetes (D) is used to meet the energy demand associated with Ex, and to identify the mechanisms involved.

METHODS
3 weeks old mice overexpressing cardiac aldosterone system (AS) and their controls (WT) were made diabetic by enriched fat and sucrose diet. After 4 months of diet, diabetic mice and their controls were subjected to 2 months of Ex on treadmill (3 sessions/week). Results: Cardiac function was not affected by Ex. The Ex led to cardiac hypertrophy in AS-D-Ex mice (+15 % in AS-D-Ex vs AS-D, P<0.01) while it improved the basic parameters of WT-D-Ex vs WT-D (body weight: -15 %, blood glucose: -15%, resistance to insulin:-50%). Interestingly, the Ex revealed a defect in AS mice: the cumulative distance traveled by AS mice, with or without type 2 D was 30% lower than in WT mice (p < 0.01). In addition, a 75% mortality was observed in AS mice (diabetic or not) submitted to the Ex, in contrast to WT mice. These results demonstrate that AS mice, unfit to Ex, developed a pathological hypertrophy. In contrast to the observed baseline responses, the Ex did not phosphorylate and thus did not activated the Akt pathway in AS-D-Ex mice (NS vs AS-D), signing the absence of activation of the physiological pathway of cardiac hypertrophy.

CONCLUSION
These results demonstrate a deleterious effect of cardiac aldosteronism in response to Ex, regardless of diabetic context, thus underlining that the microangiogenesis observed in the AS-D mice prevented neither the inability to Ex nor mortality. This suggests that the proangiogenic effect of cardiac hyperaldosteronism associated with type 2 diabetes is not enough to cope with this overload of cardiac output associated with the physical exercise.