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Transient receptor potential vanilloid type‐1 (TRPV‐1) channels contribute to cutaneous thermal hyperaemia in humans
Author(s) -
Wong Brett J.,
Fieger Sarah M.
Publication year - 2010
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2010.195511
Subject(s) - axon reflex , trpv , transient receptor potential channel , capsazepine , chemistry , trpv1 , microdialysis , vasodilation , microneurography , capsaicin , anesthesia , medicine , blood pressure , heart rate , baroreflex , receptor , biochemistry , extracellular
The initial, rapid increase in skin blood flow in response to direct application of heat is thought to be mediated by an axon reflex, which is dependent on intact cutaneous sensory nerves. We tested the hypothesis that inhibition of transient receptor potential vanilloid type 1 (TRPV‐1) channels, which are putative channels located on sensory nerves, would attenuate the skin blood flow response to local heating in humans. Ten subjects were equipped with four microdialysis fibres which were randomly assigned one of four treatments: (1) vehicle control (90% propylene glycol + 10% lactated Ringer solution); (2) 20 m m capsazepine to inhibit TRPV‐1 channels; (3) 10 m m l ‐NAME to inhibit NO synthase; and (4) combined 20 m m capsazepine + 10 m m l ‐NAME. Following baseline measurements, the temperature of skin heaters was increased from 33°C to 42°C at a rate of 1.0°C every 10 s and local temperature was held at 42°C for 20–30 min until a stable plateau in skin blood flow was achieved. An index of skin blood flow was measured directly over each microdialysis site via laser‐Doppler flowmetry (LDF). Beat‐by‐beat blood pressure was measured via photoplethysmography and verified via automated brachial auscultation. At the end of the local heating protocol, temperature of the heaters was increased to 43°C and 28 m m nitroprusside was infused to achieve maximal vasodilatation. Cutaneous vascular conductance (CVC) was calculated as LDF/mean arterial pressure and normalized to maximal values (%CVC max ). Initial peak in capsazepine (44 ± 4%CVC max ), l ‐NAME (56 ± 4%CVC max ) and capsazepine + l ‐NAME (32 ± 6%CVC max ) sites was significantly attenuated compared to control (87 ± 5%CVC max ; P < 0.001 for all conditions). The plateau phase of thermal hyperaemia was significantly attenuated in capsazepine (73 ± 6%CVC max ), l ‐NAME (47 ± 5%CVC max ) and capsazepine + l ‐NAME (31 ± 7%CVC max ) sites compared to control (92 ± 5%CVC max ; P < 0.001 for all conditions). These data suggest TRPV‐1 channels contribute substantially to the initial peak and modestly to the plateau phases of thermal hyperaemia. These data further suggest a portion of the NO component of thermal hyperaemia may be due to activation of TRPV‐1 channels.