Maximum skin hyperaemia induced by local heating: possible mechanisms.
BACKGROUND
Maximum skin hyperaemia (MH) induced by heating skin to > or = 42 degrees C is impaired in individuals at risk of diabetes and cardiovascular disease. Interpretation of these findings is hampered by the lack of clarity of the mechanisms involved in the attainment of MH.


METHODS
MH was achieved by local heating of skin to 42-43 degrees C for 30 min, and assessed by laser Doppler fluximetry. Using double-blind, randomized, placebo-controlled crossover study designs, the roles of prostaglandins were investigated by inhibiting their production with aspirin and histamine, with the H1 receptor antagonist cetirizine. The nitric oxide (NO) pathway was blocked by the NO synthase inhibitor, NG-nitro-L-arginine methyl esther (L-NAME), and enhanced by sildenafil (prevents breakdown of cGMP).


RESULTS
MH was not altered by aspirin, cetirizine or sildenafil, but was reduced by L-NAME: median placebo 4.48 V (25th, 75th centiles: 3.71, 4.70) versus L-NAME 3.25 V (3.10, 3.80) (p = 0.008, Wilcoxon signed rank test). Inhibition of NO production (L-NAME) resulted in a more rapid reduction in hyperaemia after heating (p = 0.011), whereas hyperaemia was prolonged in the presence of sildenafil (p = 0.003). The increase in skin blood flow was largely confined to the directly heated area, suggesting that the role of heat-induced activation of the axon reflex was small.


CONCLUSIONS
NO, but not prostaglandins, histamine or an axon reflex, contributes to the increase in blood flow on heating and NO is also a component of the resolution of MH after heating.
Institute of Biomedical and Clinical Sciences, Peninsula Medical School, Exeter, UK.
Kim M
KM
Gooding
Michael M
MM
Hannemann
John E
JE
Tooke
Geraldine F
GF
Clough
Angela C
AC
Shore
D001241:Aspirin / Q000494:pharmacology; D017332:Cetirizine / Q000494:pharmacology; D018592:Cross-Over Studies; D006152:Cyclic GMP / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004311:Double-Blind Method; D005260:Female; D006632:Histamine / Q000378:metabolism; D039563:Histamine H1 Antagonists, Non-Sedating / Q000494:pharmacology; D006358:Hot Temperature; D006801:Humans; D006940:Hyperemia / Q000000981:diagnostic imaging / Q000378:metabolism*; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism; D011687:Purines; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D000068677:Sildenafil Citrate; D012867:Skin / Q000098:blood supply / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D013450:Sulfones; D014463:Ultrasonography
D016861:Cyclooxygenase Inhibitors; D039563:Histamine H1 Antagonists, Non-Sedating; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011453:Prostaglandins; D011687:Purines; D013450:Sulfones; D009569:Nitric Oxide; D006632:Histamine; D000068677:Sildenafil Citrate; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D001241:Aspirin; D019331:NG-Nitroarginine Methyl Ester; D017332:Cetirizine