Isometric handgrip (IHG) training lowers resting blood pressure (BP) in both hypertensives and normotensives, yet the effect of training dose on the magnitude of reduction and the mechanisms associated with the hypotensive response are elusive. We investigated, in normotensive women, the effects of two different doses of IHG training on resting BP, and explored improved resistance vessel endothelial function and heart rate variability (HRV) as potential mechanisms of BP reduction. Resting BP, HRV, and resistance vessel endothelial function (venous strain-gauge plethysmography with reactive hyperemia) were assessed in 32 women before and after 4 and 8 weeks of 3×/week (n = 12) or 5×/week (n = 11) IHG training (four, 2-min unilateral contractions at 30 % maximal voluntary contraction), or 0×/week control (n = 9). IHG training decreased systolic BP in the 3×/week (94 ± 6 to 91 ± 6 to 88 ± 5 mmHg, pre- to mid- to post-training; P < 0.01) and 5×/week (97 ± 11 to 90 ± 9 to 91 ± 9 mmHg, P < 0.01) groups, concomitant with increased forearm reactive hyperemic blood flow (26 ± 7 to 30 ± 8 to 36 ± 9 mL/min/100 mL tissue, P < 0.01; and 26 ± 7 to 29 ± 7 to 38 ± 13 mL/min/100 mL tissue, P < 0.01, respectively), yet both remained unchanged in the control group. No changes were observed in diastolic BP, mean arterial BP, or any indices of HRV in any group (all P > 0.05). In conclusion, IHG training lowers resting systolic BP and improves resistance vessel endothelial function independent of training dose in normotensive women.