Previous work from our laboratory demonstrated that isometric handgrip (IHG) training improved local, endothelial-dependent vasodilation in medicated hypertensives (22, 23). We investigated whether changes in the capacity of smooth muscle to dilate (regardless of endothelial factors) influenced this training-induced change, and examined the acute vascular responses to a single bout of IHG. Seventeen subjects performed 4, 2-min unilateral IHG contractions at 30% of maximal voluntary effort, 3X/week for 8 weeks. Pre- and post-training, brachial artery flow mediated dilation (FMD, an index of endothelial-dependent vasodilation) and nitroglycerin -mediated maximal vasodilation (an index of endothelial-independent vasodilation) were measured in the exercised arm using ultrasound prior to and immediately following acute IHG exercise. IHG training resulted in improved resting brachial FMD (p < 0.01) and no change in nitroglycerin-mediated maximal vasodilation. Pre- and post-training, brachial artery FMD decreased following an acute bout of IHG exercise (normalized to peak shear rate, pre-, before-IHG exercise: 0.01 + 0.002, after-IHG exercise: 0.008 + 0.002 %/s^-1; post-, before-IHG exercise: 0.020 + 0.003, after-IHG exercise: 0.010 + 0.003 %/s^-1; p < 0.01). Post-training, resting brachial artery FMD improved yet nitroglycerin-mediated maximal vasodilation was unchanged in persons medicated for hypertension. This suggests that the training-induced improvements in resting brachial artery FMD were not due to underlying changes in the forearm vasculature. Acute IHG exercise attenuated brachial artery FMD, and although this impairment may be interpreted as hazardous to medicated hypertensives with already dysfunctional endothelium, the effects appear transient as repeated exposure to the IHG stimulus improved resting endothelial-dependent vasodilation.