Role of alpha2C-adrenoceptors in the reduction of skin blood flow induced by local cooling in mice.
OBJECTIVE
The reduction of skin blood flow induced by local cooling results from a reflex increase in sympathetic output and an enhanced vasoconstrictor activity of cutaneous vessels. The present study investigated the latter local response in vivo in tetrodotoxin-treated mice, in which the sympathetic nerve tone was abolished.


METHODS
Male ddY mice, anaesthetized with pentobarbitone, were treated with tetrodotoxin and artificially ventilated. The plantar skin blood flow (PSBF) was measured by laser Doppler flowmetry.


RESULTS
Cooling the air temperature around the left foot from 25 to 10 degrees C decreased the PSBF of the left foot. Bunazosin, an alpha (1)-adrenoceptor antagonist, RS79948, an alpha (2)-adrenoceptor antagonist, and MK-912, an alpha (2C)-adrenoceptor antagonist, all significantly inhibited the cooling-induced reduction of PSBF; the inhibition by bunazosin was relatively small compared with that by RS79948 and MK-912. The response was not affected by guanethidine or bretylium, but was diminished in adrenalectomized mice. An intra-arterial injection of clonidine, an alpha (2)-adrenoceptor agonist, to the left iliac artery of adrenalectomized mice caused a transient decrease in PSBF, which was significantly augmented at 10 degrees C. MK-912 suppressed only the augmented portion at 10 degrees C. Y-27632, H-1152 and fasudil, Rho kinase inhibitors, also inhibited the cooling-induced reduction of PSBF. RS79948 caused no further reduction of the cooling-induced response after the inhibition by Y-27632.


CONCLUSIONS
Local cooling-induced reduction of skin blood flow in mice primarily results from increased reactivity of alpha (2C)-adrenoceptors to circulating catecholamines, in which the Rho/Rho kinase pathway is involved.
Honda
M
M
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422-8526, Japan.
Suzuki
M
M
Nakayama
K
K
Ishikawa
T
T
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000315:Adrenalectomy; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D001808:Blood Vessels / Q000201:enzymology / Q000294:innervation / Q000378:metabolism; D001833:Body Temperature Regulation / Q000187:drug effects / Q000502:physiology*; D003000:Clonidine / Q000494:pharmacology; D003080:Cold Temperature; D006339:Heart Rate; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D017078:Laser-Doppler Flowmetry; D008297:Male; D051379:Mice; D009287:Naphthyridines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D011807:Quinolizines / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism*; D012018:Reflex; D012039:Regional Blood Flow; D012867:Skin / Q000098:blood supply*; D012881:Skin Temperature / Q000187:drug effects; D013564:Sympathetic Nervous System; D013779:Tetrodotoxin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D054460:rho-Associated Kinases
C459092:2-methyl-1-((4-methyl-5-isoquinolinyl)sulfonyl)homopiperazine; C547775:Adra2c protein, mouse; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000577:Amides; D000779:Anesthetics, Local; D047908:Intracellular Signaling Peptides and Proteins; D007546:Isoquinolines; D009287:Naphthyridines; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011807:Quinolizines; C104875:RS 79948-197; D018341:Receptors, Adrenergic, alpha-2; C054290:L 657743; C108830:Y 27632; D013779:Tetrodotoxin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D003000:Clonidine; C049347:fasudil