Modulation of hydrogen sulfide synthesis improve 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 NO-synthase in diabetes. The aim of work is to investigate the effect of modulation of hydrogen sulfide 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, iNOS and cNOS activities, endothelium-dependent vasorelaxation of the aortic rings, and heart function were studied. We demonstrate that our combination increased H2S syntheses by 13 times and cNOS activity by 5 times in the heart tissue of diabetic rats. Increasing NO and H2S production caused improving and restoration of endothelium-dependent relaxation of aorta, effective arterial elastance, and diastolic heart function in diabetic rats. The endothelium-dependent relaxation increased by 2.4 times; effective arterial elastance decreased by 47%. The end-diastolic myocardial stiffness decreased by 2.2 times. Thus, modulation of hydrogen sulfide synthesis leads to increased activity cNOS by 5 times in the cardiovascular system. Increasing NO and H2S production restored endothelium-dependent relaxation of aorta and improved heart function in diabetes.

Muscle metaboreflex-induced increases in effective arterial elastance: effect of heart failure

Dynamic exercise elicits robust increases in sympathetic activity in part due to muscle metaboreflex activation (MMA), a pressor response triggered by activation of skeletal muscle afferents. MMA during dynamic exercise increases arterial pressure by increasing cardiac output via increases in heart rate, ventricular contractility, and central blood volume mobilization. In heart failure, ventricular function is compromised, and MMA elicits peripheral vasoconstriction. Ventricular-vascular coupling reflects the efficiency of energy transfer from the left ventricle to the systemic circulation and is calculated as the ratio of effective arterial elastance ( Ea) to left ventricular maximal elastance ( Emax). The effect of MMA on Ea in normal subjects is unknown. Furthermore, whether muscle metaboreflex control of Ea is altered in heart failure has not been investigated. We utilized two previously published methods of evaluating Ea [end-systolic pressure/stroke volume ( EaPV)] and [heart rate × vascular resistance ( EaZ)] during rest, mild treadmill exercise, and MMA (induced via partial reductions in hindlimb blood flow imposed during exercise) in chronically instrumented conscious canines before and after induction of heart failure via rapid ventricular pacing. In healthy animals, MMA elicits significant increases in effective arterial elastance and stroke work that likely maintains ventricular-vascular coupling. In heart failure, Ea is high, and MMA-induced increases are exaggerated, which further exacerbates the already uncoupled ventricular-vascular relationship, which likely contributes to the impaired ability to raise stroke work and cardiac output during exercise in heart failure.