Cardio-Humoral Actions of the Phosphodiesterase-V Inhibitor Vardenafil in Experimental Diabetic Cardiomyopathy

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Background: Diabetic cardiomyopathy (DMC) is defined as the presence of left ventricular (LV) dysfunction (systolic and/or diastolic) in diabetes mellitus without a prior history of coronary artery disease, hypertension or valvular disease. Cyclic guanosine 3’,5’-monophosphate (cGMP) the second messenger of the natriuretic peptide system and the nitric oxide system plays an important role in the preservation of myocardial function. We determined the cardio-humoral effects of chronic treatment with the phosphodiesterase-V inhibitor (PDEVI) vardenafil in rat model of DMC. Methods: Diabetes mellitus was induced in male Wistar rats by a single dose of intra peritoneal injection of Streptozotocin (65 mg/Kg). Four weeks after establishing diabetes, the treatment group (n=6) received a suspension of vardenafil daily by gavage for two months at the dose of 5mg/kg/day and the diabetic control group (n=12) received no treatment. A non-diabetic control group (n=13) was maintained as positive control. Echocardiography was used to assess LV structure and function. Plasma humoral profile was assessed and at 3 months, the hearts were harvested for analysis. Results: As compared with non-diabetic controls, the diabetic 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) (p<0.05). These changes were associated with increased plasma BNP, renin and aldosterone levels. The LVH decreased and LV dysfunction improved significantly with vardenafil treatment as compared to the diabetic controls (p<0.05) and was associated with decreases in plasma BNP, renin and aldosterone levels. Conclusion: PDEV inhibition with Vardenafil attenuated LVH and improved LV systolic and diastolic myocardial function, associated with suppression of aldosterone and renin in a rat model of experimental DM cardiomyopathy. These findings suggest that both the PDEV and renin-aldosterone systems are involved in the pathophysiology of DMC.