Influence of prostaglandins and endothelial-derived hyperpolarizing factors on brachial and popliteal...

Heterogeneous flow-mediated dilation (FMD) and low-flow-mediated constriction (L-FMC) responses have been reported between upper- and lower-limb arteries. Radial artery L-FMC, but not FMD, responses are blunted when endothelial-derived hyperpolarizing factors (EDHFs) or prostaglandin production is inhibited in young adults. However, it is unknown if these mechanisms similarly impact endothelial-dependent responses in the brachial (BA) and popliteal (POP) arteries. We tested whether BA- and POP-L-FMC and FMD would be influenced by independent EDHF and prostaglandin inhibition. Eighteen participants (23 ± 3 yr; 6♀) completed three randomized and double-blinded ultrasound assessments following ingestion of an opaque capsule containing maltodextrin (control), 150 mg of fluconazole (EDHF inhibition), or 500 mg of aspirin (prostaglandin inhibition). POP resting diameter was reduced following fluconazole administration (6.13 ± 0.63 mm vs. 6.19 ± 0.65 mm in control, P = 0.03). Compared with control, fluconazole also blunted the relative L-FMC responses in both the BA (-2.1 ± 0.8% vs. -0.8 ± 1.0%, P = 0.001) and POP (-1.7 ± 1.1% vs. -0.8 ± 0.9%, P = 0.009). In contrast, aspirin did not impact either the BA (-1.9 ± 0.7%) or POP-L-FMC (-1.3 ± 0.6%) responses (both, P > 0.35). The FMD response was unchanged following fluconazole or aspirin administration in either artery (both, P > 0.36). Our findings demonstrate that EDHF mediates L-FMC responses in both the brachial and popliteal arteries. Complementary to the nitric oxide-mediated FMD response, L-FMC appears to provide information regarding the EDHF pathway. Future research should uncover if these mechanisms impact older adults and/or patient populations characterized by vascular endothelial dysfunction associated with low aerobic fitness and habitual physical activity levels.NEW & NOTEWORTHY We compared changes in upper- and lower-limb artery endothelial-dependent vasodilatory and vasoconstrictor responses between control, prostaglandin inhibition, and endothelial-derived hyperpolarizing factor inhibition conditions. Neither prostaglandins nor endothelial-derived hyperpolarizing factor influenced flow-mediated dilation responses in either the brachial or popliteal artery. In contrast, endothelial-derived hyperpolarizing factor, but not prostaglandins, reduced resting brachial artery blood flow and shear rate and resting popliteal artery diameter, as well as low-flow-mediated constriction responses in both the popliteal and brachial arteries.