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Objective The reactivity of conduit vessels such as the brachial artery is important in influencing arterial diameter, and subsequently, blood flow. Flow‐mediated dilation (FMD) measures vessel reactivity. The increase in shear stimuli from transient arterial occlusion enhances arterial diameter in an endothelial‐dependent manner, and this is thought to be impaired in individuals with congenital heart disease (CHD). Isometric handgrip (IHG) exercise is a proposed intervention to improve vessel reactivity by optimizing the shear stimuli to provoke changes in arterial diameter. Indeed, IHG training has been found to improve FMD in healthy adults and children. Whether IHG training improves endothelial dysfunction in CHD remains unknown. Improving vessel reactivity in the young becomes increasingly important in optimizing vascular health into adulthood. The effects of acute IHG exercise on the brachial artery were examined in children with CHD. Hypothesis We tested the hypothesis that acute IHG exercise would increase FMD in children with CHD. Methods Four subjects with CHD (mean, 13 ± 1 year, 3 female) completed a single session of 4 × 2 mins of acute IHG (30% maximum voluntary contraction using the right hand) with 1‐min rest intervals between bouts. Before and after IHG exercise, the right brachial artery was imaged with Duplex ultrasound using a 1‐min baseline, 5 mins of forearm circulatory occlusion, followed by 3 mins of cuff deflation. Blood pressure and heart rate were measured continuously. Results Pre‐FMD (baseline) mean arterial pressure (pre: 102 ± 17 mmHg vs. post: 110 ± 16 mmHg, p = 0.496) and heart rate (pre: 75 ± 13 bpm vs. post: 66 ± 5 bpm, p = 0.253) were not different. Baseline brachial artery diameter increased following acute IHG in 3 of 4 subjects (pre: 3.11 ± 0.45 mm vs. post: 3.23 ± 0.39 mm, Cohen’s d = 0.3). Peak shear rate was greater post‐IHG in 3 of 4 subjects (pre: 995 ± 346 sec‐1vs. post: 1158 ± 501 sec‐1, Cohen’s d = 0.4). FMD% (4.7% vs. 6.3% and 8.2% vs. 10.5%) and FMD% normalized to shear rate area under the curve (AUC) ratio (2.2E‐5 vs. 7.4E‐5 a.u. and 3.1E‐5 vs. 4.3E‐5 a.u., Cohen’s d = 2.0) increased post‐IHG in 2 of 4 subjects. When brachial artery diameter increased, peak shear rate, FMD%, and FMD% normalized to shear rate AUC improved post‐IHG in 2/3 subjects whereas subject four showed a decrease in brachial artery diameter, FMD% and FMD% normalized to shear rate AUC, with the exception of peak shear rate post‐IHG. Conclusion Favorable changes in brachial artery diameter, peak shear rate, FMD% and FMD% normalized to shear rate AUC following acute IHG may be a promising intervention for improving vascular tone and endothelial function in children with CHD.

Introduction Competing influences regulate blood flow control in the brain. In the skeletal muscle vasculature, purinergic ATP signaling attenuates α1‐adrenergic and peptidergic‐induced vascular smooth muscle contraction (i.e., phenomenon referred to as functional sympatholysis); however, whether this occurs in the cerebrovasculature remains unknown. The purpose of this experiment was to examine the effect of ATP on vascular responses to α1‐adrenergic‐ and peptidergic‐receptor activation in cerebral arteries. We hypothesized that ATP would attenuate the α1‐adrenergic‐ and peptidergic‐mediated vasocontraction in isolated pial arteries. Methods Female pigs (n=5) were euthanized and their brains harvested. Thereafter, 1A branches of the middle cerebral artery were dissected for wire‐myography. Dose‐response curves for the α1‐adrenergic agonist phenylephrine (PE;1e‐10‐1e‐4M) and the peptidergic agonist neuropeptide Y (NPY;1e‐12‐1e‐6M) were performed in the absence or presence of ATP (1e‐6M). Paired one‐tailed t‐tests were used to compare the overall magnitude of contraction (area under the curve; AUC) and physiological maximal responses between conditions. Results Data are mean±SD. The AUC of PE‐mediated cerebral vasocontraction was attenuated by ATP (untreated=67±25 vs. ATP pre‐treatment=33±23 AU; p=0.03). However, the mean reduction in the maximal response to PE in arteries pre‐treated with ATP was not significant (untreated=43±15 vs. ATP pre‐treatment=27±11%; p=0.10). The AUC (untreated=62±31 vs. ATP pre‐treatment=37±23 AU) as well as maximal NPY‐mediated cerebral vasocontraction (untreated=65±20 vs. ATP pre‐treatment=49±21%) was attenuated by ATP (all p≤0.05). Conclusion These data indicate ATP attenuates PE‐ and NPY‐mediated vasocontraction in isolated pial arteries. Thus, similar to the skeletal muscle vasculature, purinergic signaling attenuates vasoreactivity to α1‐adrenergic and peptidergic receptor activation in the cerebrovasculature. Functional sympatholysis may assist in coupling cerebral blood flow to brain metabolism under basal conditions as well as in the setting of heightened sympatho‐excitation.

Introduction Aging is associated with increased sympathetic nerve activity (SNA) and reduced vasoreactivity. Cold pressor test (CPT) increases SNA and may thus counteract exercise‐induced local vasodilation. We tested the hypothesis that older adults would exhibit less vasoreactivity following acute rhythmic handgrip (HG) exercise coupled with CPT compared to young adults. Methods Twenty older adults (60 ± 5 yrs; 10F) and 12 young adults (24 ± 4 yrs; 6F) underwent a bed study of 5‐min baseline, 4‐min 40% MVC rhythmic HG, 2‐min CPT superimposed with HG (HG+CPT), and 5‐min recovery. Brachial artery measures included diameter (B‐mode Doppler), blood velocity (pulsed‐wave Doppler), blood flow, shear rate, and resistance, as well as heart rate (HR, ECG) and mean arterial pressure (MAP, finger plethysmography). Vasoreactivity was assessed with minimum and peak values within 60 s post‐HG+CPT. Statistics included mixed methods ANOVA and ANCOVA (p< 0.05). Results Brachial blood flow and velocity had condition effects (p < .001) but no interaction or group effects (p > .05). Both groups increased blood flow and velocity from baseline to HG (Δ201 ± 148 mL/min, p < .001; Δ26 ± 11 cm/s, p < .001) and further increased during HG+CPT (Δ47 ± 96 mL/min, p= .021; Δ3 ± 7 cm/s, p= .017). Post‐HG+CPT blood flow and velocity decreased (Δ‐194 ± 208 mL/min, p< .001; Δ‐20 ± 19 cm/s, p< .001) and then increased to peak values greater than HG+CPT (Δ73 ± 177 mL/min, p< .001; Δ13 ± 10 cm/s, p< .001) before decreasing to above baseline levels after 5‐min (Δ26 ± 52 mL/min, p= .016; Δ3 ± 5 cm/s, p= .002). A group × condition interaction (p = .042) revealed greater brachial diameter in older (4.27 ± 0.76 mm) compared to young adults (3.24 ± 0.81 mm, p = .002) at each condition (all p < .05). Diameter did not change during HG or HG+CPT (all p > 0.05). Post‐HG+CPT diameter first decreased in young adults (2.69 ± 0.91 mm, p = .003) and then increased to a peak value in both young (3.61 ± 0.90 mm; p = .006) and older adults (4.58 ± 0.88 mm, p = .003). Diameter returned to baseline after 5‐min in young (3.35 ± 0.78 mm, p = .154) and older adults (4.17 ± 0.76 mm, p = .329). Resistance was not different between groups (p = .147) but dropped during HG (Δ‐9 ± 10 mmHg/mL/min, p< .001) and remained low during HG+Cold (Δ1 ± 11 mmHg/mL/min, p= .334) before returning to baseline levels after 5‐min (Δ‐2 ± 7 mmHg/mL/min, p< .196). Shear rate (Δ279 ± 180 s‐1, p< .001), MAP (Δ8 ± 6 mmHg, p< .001), and HR (Δ8 ± 6 bpm, p< .001) increased from baseline to HG in all participants. HG+CPT further increased shear rate (Δ38 ± 94 s‐1, p= .005), MAP (Δ9 ± 7 mmHg, p< .001) and HR (Δ4 ± 7 bpm, p= .002) before decreasing to above baseline levels of shear rate (Δ30 ± 54 s‐1, p= .003) and MAP after 5‐min (Δ2 ± 6 mmHg, p= .034). HR returned to baseline in older adults (Δ0 ± 3 bpm, p= .656) and fell below baseline in young adults (Δ‐3 ± 4 bpm, p= .008). MAP (109 ± 11 vs. 100 ± 11 mmHg, pooled p= .039) was greater in older compared to young adults across conditions. Conclusion Imm...