Arteriolar Endothelial Dysfunction Is Restored in Ischaemic Muscles by Chronic Electrical Stimulation

Abstract

Chronic intermittent electrical stimulation (15 min on, 85 min off, seven times per day) eliminated endothelial dysfunction of pre-capillary arterioles in ischaemic rat ankle flexor muscles. Responses to acetylcholine were restored from constriction to dilation, and the reduced dilation to bradykinin was corrected by 1 week of stimulation. Administration of the NOS inhibitor N^ω-nitro-L-arginine for 1 week impaired arteriolar reactivity in a similar way to ischaemia, and dilator function was likewise restored by chronic stimulation. This suggests that nitric oxide production in the microcirculation is depressed by chronic ischaemia and that chronic electrical stimulation can specifically reverse this deficit. Stimulation applied to ischaemic muscles for 2 weeks also increased the numbers of microvessels immunostained for α-smooth muscle actin and the numbers of eNOS-positive microvessels and capillaries. These findings help to elucidate the mechanism of the beneficial effect of exercise in the treatment of peripheral vascular diseases by showing that muscle activity can improve both function and structural capacity of the microvasculature.

Suppressed hindlimb perfusion in Rac2−/− and Nox2−/− mice does not result from impaired collateral growth

“…Other studies (34,56) have shown that perfusion subsequent to femoral artery occlusion is not correlated with capillarity. Studies have shown that chronic reductions in flow and pressure can result in enhanced constriction and inward remodeling characterized by wall thinning (1,6,8,17,19,41,49,50,64,67), characteristics that occur in human critical limb ischemia (17)(18)(19). Thus, the profound decrease in distal microvascular flow and pressure could result in similar decompensatory events in the precapillary arterioles and small arteries that control the majority of microvascular resistance (3,27,42,77).…”

Ischemia Impairs Vasodilation in Skeletal Muscle Resistance Artery

“…Unfortunately, chronic ischemia leads to vasodilatory dysfunction. Ischemic arterioles in the lower leg have impaired functional vasodilation, which could be explained by impaired endothelial-dependent dilation [69,70]. Similar results were found in rat collateral arteries in vitro [71].…”

“…Also, with improvements made in superfusion, the effects of age using cell-specific vasoactive agents can be addressed. Exercise is also a possible treatment to be attempted, as previous research has showed improvement in endothelial function [41,70,71] following exercise. It is still unclear what specifically impairs vascular function in ischemic conditions; it is the goal of this research to solve those questions.…”

Low-Frequency Electrical Stimulation Increases Muscle Strength and Improves Blood Supply in Patients With Chronic Heart Failure

“…Thus, the previously mentioned beneficial effects of LFES on vascular function are most probably related to the effect of increased pulsatile flow on the vessel's endothelial layer. 54,55 It is likely that the LFESinduced changes in blood flow by long-term electrical stimulation are related to modification of endothelial function, and thus may be mostly NO-dependent, but as mentioned earlier, additional mechanisms cannot be excluded, especially the possible growth enhancement of new vessel collaterals, as occurs after physical exercise training. 56 The contribution of LFES on vascular remodelling observed in this study may be seen in the insignificant increase of the inner diameter of the right femoral artery at the end of the 6 th week of stimulation.…”