Abstract 1162: Effect of Phosphodiesterase-V Inhibitor Vardenafil on Myocardial Fibrosis and Cardio-Humoral Actions in Experimental Diabetic Cardiomyopathy
Background: Diabetes mellitus (DM) is a major risk factor for left ventricular (LV) dysfunction and cardiac fibrosis. Cyclic guanosine monophosphate (cGMP), the second messenger of the natriuretic peptide (NP) and nitric oxide systems, plays an important role in the preservation of myocardial function. We examined the antifibrotic and cardio-humoral effects of chronic treatment with the phosphodiesterase-5 inhibitor (PDEVI) vardenafil in a rat model of Diabetic cardiomyopathy (DCM).
Methods: DM was induced in male Wistar rats by a single intra peritoneal injection of Streptozotocin (65 mg/Kg). Four weeks after establishing DM, the treatment group (n=5) received a suspension of vardenafil daily by gavage for two months at 5 mg/kg/day and the diabetic group (n=6) received no treatment. A non-diabetic control (n=6) was maintained as positive control. Plasma humoral profile was assessed and at 3 months, after echocardiography, myocardium was harvested and stained with Picrosirius Red to assess the infiltration of collagen. *p<0.05.
Results: Percent collagen infiltration increased significantly in the LV of DM rats (9.0±2*) as compared to non-DM controls (3.3±2). Vardenafil treated DM rats showed reduced collagen infiltration (5.6±3.6*). Compared to non-DM controls, the DM controls had LV hypertrophy (LVH) (0.25±0.01* vs 0.18±0.01 LV body weight %) and systolic and diastolic myocardial dysfunction as measured by peak circumferential contraction strains (Cs-C) (10.8±0.7* vs 14.3±0.6 %), strain rates (Csr-C) (2.3±0.1 vs 3.9±0.3 s −1) and early diastolic strain rates (Csr-E) (2.6±0.2* vs 3.9±0.3 s −1). These changes were associated with increased plasma BNP, renin and aldosterone levels. LVH decreased* and LV function improved* with vardenafil treatment as compared to the DM controls and was associated with decreases in plasma BNP, renin and aldosterone levels.
Conclusion: DCM is characterized by LV dysfunction and LVH with infiltration of collagen in the LV. Vardenafil treatment reduced fibrosis, attenuated LVH, improved LV systolic and diastolic myocardial function with suppression of aldosterone and renin. These findings suggest that both the PDEV, cGMP and renin-aldosterone systems are involved in the pathophysiology of DCM.