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The isometric handgrip training (IHT) has been emerging as an alternative approach for blood pressure (BP) reduction in hypertensive patients. However, the mechanisms underlying the reductions in BP after IHT are poorly known. Thus, the aim of this study was to analyze the vascular effects of IHT in hypertensive patients. A randomized controlled trial was conducted with 33 hypertensive patients (61 ± 2 y.o.; 67% female) who were randomly assigned to two groups: IHT or control group. The IHT group has completed three weekly sessions of isometric handgrip (4 × 2  min sets, alternating the hands at 30% of maximal voluntary contraction). Before and after a period of 12 weeks BP, arterial stiffness, central and peripheral pulse wave velocity (PWV) and endothelial function were measured. The IHT approach has significantly decreased systolic (∆ = −16 ± 2 vs. ∆ = −3 ± 3 mmHg, p < 0.001) and diastolic (∆ = −8 ± 2 …