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KCa channels and EETs: major contributors to cutaneous thermal hyperemia
Author(s) -
Brunt Vienna E,
Minson Christopher T
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1079.10
Subject(s) - vascular tone , chemistry , microdialysis , medicine , cyp2c9 , pharmacology , anesthesia , cytochrome p450 , cardiology , vasodilation , biochemistry , extracellular , metabolism
While it is accepted NO is responsible for ~60% of the plateau in cutaneous thermal hyperemia, a large portion of the response remains unknown. We sought to determine whether the remaining ~40% could be attributed to EDHFs via KCa channels, and whether the epoxyeicosatrienoic acids (EETs), derived via cytochrome P450, were the predominant EDHF active in the response. Four microdialysis fibers were placed in the forearm skin of 20 subjects. In Protocol 1 (n=10): (1) Control, (2) L‐NAME, (3) KCa channel inhibitor, tetraethylammonium (TEA), and (4) L‐NAME + TEA; in Protocol 2 (n=10): (1) Control, (2) L‐NAME, (3) cytochrome P450 inhibitor, sulfaphenazole, and (4) L‐NAME + Sulfaphenazole. Local heating to 42°C was performed and skin blood flow was measured with Laser Doppler flowmetry. All data are presented as % maximal cutaneous vascular conductance (CVC). All drug sites attenuated plateau CVC from the control site (85±2%) to 79±3% with sulfaphenazole, 71±3% with TEA, 39±3% with L‐NAME, 23±2% with L‐NAME + sulfaphenazole, and 13±2% with L‐NAME + TEA (not different from baseline). Furthermore, the initial peak was just 17±2% with L‐NAME + TEA. These data suggest EDHFs are responsible for the remaining 40% of the plateau phase, as administration of TEA in combination with L‐NAME abolished the majority of hyperemia. These data also suggest that EETs contribute to about half of the EDHF response. Supported by NIH Grant HL081671