Modulation of hydrogen sulfide synthesis improves heart function and endothelium-dependent vasorelaxation in diabetes

Diabetes dramatically increases the risk of cardiovascular complications. The endothelial dysfunction and diastolic heart dysfunction are associated with a decreasing level of hydrogen sulfide (H₂S) and inhibition of the activity of endothelial nitric oxide synthase (NOS) in diabetes. The aim of this study is to investigate the effect of modulation of H₂S synthesis on heart functions and vasorelaxation in diabetes. The dl-propargylglycine and l-cysteine were administered intraperitoneally. H₂S content in the heart tissue, markers of oxidative stress, inducible NOS and constitutive NOS (cNOS) activities, endothelium-dependent vasorelaxation of the aortic rings, and heart function were studied. We demonstrate that our combination increased H₂S synthesis 13 times and cNOS activity 5 times in the heart tissue of diabetic rats. Increasing NO and H₂S production caused improvement and restoration of endothelium-dependent relaxation of aorta, effective arterial elastance, and diastolic heart function in diabetic rats. The endothelium-dependent relaxation increased 2.4 times; effective arterial elastance decreased by 47%. The end-diastolic myocardial stiffness decreased 2.2 times. Thus, modulation of H₂S synthesis leads to increased cNOS activity by up to 5 times in the cardiovascular system. Increasing NO and H₂S production restored endothelium-dependent relaxation of aorta and improved heart function in diabetes.