Promotion of Aerobic Exercise Induced Angiogenesis Is Associated With Decline in Blood Pressure in Hypertension

Microvascular rarefaction plays a key role in hypertension-induced microvascular organ damage. Aerobic exercise (AE) can reduce blood pressure and improve endothelial progenitor cell (EPC) function in hypertension. Here, we investigate the effect of AE on hypertensive microvascular rarefaction and its association with the improvement of EPCs angiogenic capacity and blood pressure decline. One hundred forty-one patients with essential hypertension without any antihypertension medication were randomized into AE group (n=75) and control group (n=66). AE was performed for 5 days a week and 12 weeks in total using cycle ergometer with moderate intensity. Hypertensive subjects displayed decreased skin capillary density, retinal capillary density, and increased retinal nonperfused area, which were related to blood pressure. AE markedly increased capillary density skin capillary density: (43.14±4.66)/mm 2 versus (39.86±4.92)/mm 2 , P <0.001; retinal capillary density: (54.51±2.35)% versus (52.85±2.9)%, P <0.001; and decreased the nonperfused area (0.09±0.07) mm 2 versus (0.12±0.07) mm 2 , P <0.01, which was accompanied with the increased angiogenic capacity of EPCs. Interestingly, AE significantly reduced systolic blood pressure ( P <0.01), which was independently correlated with skin capillary density (β=−0.47, t =−3.06, P =0.004) and retinal capillary density (β=−0.46, t =−3.01, P =0.005). Furthermore, AE accelerated EPC angiogenic ability via inhibiting NOTCH 1 expression and elevating its downstream Akt/eNOS (endothelial nitric oxide synthase) signaling in hypertension. Blockage of NOTCH 1/Akt/eNOS signaling almost completely abolished the protective effect of AE on EPC function. The current study demonstrates for the first time that AE can lower blood pressure and reduce microvascular rarefaction in hypertension, which is partially due to restoration of angiogenesis capacity of EPCs via NOTCH 1/Akt/eNOS signaling pathway.