BackgroundHeart failure with preserved ejection fraction (HFpEF) is associated with symptoms of exercise intolerance, which may correspond to disease‐related changes in the peripheral circulation. A small muscle mass (dynamic handgrip, HG) exercise that evokes minimal cardiopulmonary stress was utilized to concomitantly evaluate exercising muscle blood flow and conduit vessel endothelium‐dependent vasodilation in patients with HFpEF compared to hypertensive controls (CON).MethodsWe evaluated heart rate (HR), stroke volume (SV), cardiac output (CO), mean arterial pressure (MAP), and brachial artery blood velocity and diameter in CON (n = 25, 52 ± 7 y, BMI 30 ± 6 kg/m2) and patients with HFpEF (n = 25, 69 ± 10 y, BMI 33 ± 6 kg/m2) during dynamic HG exercise (15, 30, and 45% MVC, 1 contraction/sec). Brachial artery blood flow and vascular conductance were determined to quantify the hemodynamic response to HG exercise, and changes in brachial artery diameter were evaluated to assess conduit vessel vasodilatory capacity.ResultsWhile HR modestly increased in both groups at 45% MVC (10 ± 2 and 8 ± 2 bpm compared to rest, HFpEF and Control), SV and CO were unchanged across exercise intensities in both groups. Brachial artery blood flow was similar between groups at the lowest exercise intensity (15% MVC: 145 ± 41 vs. 158 ± 17 ml/min, HFpEF vs. CON) but was blunted by 20–40% in HFpEF patients at higher work rates (30% MVC: 229 ± 8 vs. 274 ± 23 ml/min, 45% MVC: 283 ± 17 vs. 399 ± 34 ml/min, HFpEF vs. CON). Brachial artery vascular conductance increased to a similar degree in both groups at 15 and 30% MVC, but was blunted by ~20% at the highest exercise intensity (45% MVC: 2.74 ± 0.21 vs. 3.54 ± 0.30 ml/min/mmHg, HFpEF vs. CON). Brachial artery shear rate was similar between HFpEF and CON at all exercise intensities. Brachial artery diameter increased across work rates in both HFpEF (15% MVC: 3 ± 1%, 30% MVC: 6 ± 1%, 45% MVC: 8 ± 1%) and CON (15% MVC: 2 ± 1%, 30% MVC: 4 ± 1%, 45% MVC: 7 ± 1%), and there was no difference between groups.ConclusionsThese results provide evidence for impaired skeletal muscle blood flow during small muscle mass exercise in patients with HFpEF that cannot be attributed to a disease‐related alteration in central hemodynamics. However, brachial artery vasodilation in response to the step‐wise, sustained shear stimulus evoked during exercise was similar between groups, suggesting a preservation of endothelium‐dependent dilation in patients with HFpEF compared to their hypertensive counterparts. Together, these findings suggest an overall derangement in the regulation of muscle blood flow during exercise in patients with HFpEF that is not attributable to disease‐related changes in endothelial function.Support or Funding InformationThis project is funded in part by the National Institutes of Health (HL118313) and the U.S. Department of Veterans Affairs (RX001697, RX001418, E6910R).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.