{'fraction_non_alphanumeric': 0.054429028815368194, 'fraction_numerical': 0.04695837780149413, 'mean_word_length': 5.399317406143345, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
H2O2‐Induced Dilation in Human Adipose Arterioles: Role of Smooth Muscle K+ Channels

Hydrogen peroxide (H2O2) induces potent vasodilation in human coronary arterioles from subjects with coronary artery disease (CAD) through the activation of protein kinase G‐large conductance Ca2+‐activated K+ (BKCa) channel pathway. Because the vasodilator effect and mechanism of action of H2O2 vary among different vascular beds and species, it remains unknown whether the K+ channel‐mediated dilation is conserved in other systemic vascular beds in humans. We investigated the vasomotor effect of H2O2 and its underlying mechanism in human adipose arterioles. Arterioles (100‐200 μm) obtained from subjects without CAD were cannulated under 60 mmHg and examined for diameter changes using video microscopy. H2O2 (1‐100 µM) induced concentration‐dependent vasodilation, with maximal dilation of 95±1% at 100 µM. H2O2‐induced dilation was endothelium‐independent and markedly reduced by both paxilline, a BKCa channel blocker, and 4‐AP, a voltage‐gated K+ (KV) channel blocker (dilation at 10 μM, 19±13% vs. 72±9% in control, and 26±5% vs. 66±11% in control, respectively). We further investigated which subtype(s) of the KV1 channels (the major KV family in the vasculature) is responsible to H2O2‐induced dilation. Similar to 4‐AP, DPO‐1 (KV1.5 channel‐specific blocker) reduced dilation to 10 μM H2O2 (12±5% vs. 54±7% in control). In addition, the KV 1.3/1.5‐specific blocker Psora‐4 caused a similar rightward shift in H2O2‐induced dilation, but further reduced the maximal dilation to 100 μM H2O2 (58±5% vs. 83±5% in DPO‐1). In conclusion, H2O2 dilates human adipose arterioles from non‐CAD subjects and the dilation is mediated by both KV and BKCa channels in smooth muscle cells. The mechanism by which H2O2 activates K+ channels (especially KV channel) remains to be determined.