Role of alpha2C-adrenoceptors in the reduction of skin blood flow induced by local cooling in mice

Br J Pharmacol. 2007 Sep;152(1):91-100. doi: 10.1038/sj.bjp.0707380. Epub 2007 Jul 9.

Abstract

Background and purpose: 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.

Experimental approach: 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.

Key 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 and implications: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
  • Adrenalectomy
  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic alpha-Antagonists / pharmacology
  • Amides / pharmacology
  • Anesthetics, Local / pharmacology
  • Animals
  • Blood Pressure
  • Blood Vessels / enzymology
  • Blood Vessels / innervation
  • Blood Vessels / metabolism
  • Body Temperature Regulation / drug effects
  • Body Temperature Regulation / physiology*
  • Clonidine / pharmacology
  • Cold Temperature*
  • Heart Rate
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Isoquinolines / pharmacology
  • Laser-Doppler Flowmetry
  • Male
  • Mice
  • Naphthyridines / pharmacology
  • Protein Kinase Inhibitors / pharmacology
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / metabolism
  • Pyridines / pharmacology
  • Quinolizines / pharmacology
  • Receptors, Adrenergic, alpha-2 / drug effects
  • Receptors, Adrenergic, alpha-2 / metabolism*
  • Reflex
  • Regional Blood Flow
  • Skin / blood supply*
  • Skin Temperature* / drug effects
  • Sympathetic Nervous System
  • Tetrodotoxin / pharmacology
  • Vasoconstriction* / drug effects
  • rho-Associated Kinases

Substances

  • 2-methyl-1-((4-methyl-5-isoquinolinyl)sulfonyl)homopiperazine
  • Adra2c protein, mouse
  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Amides
  • Anesthetics, Local
  • Intracellular Signaling Peptides and Proteins
  • Isoquinolines
  • Naphthyridines
  • Protein Kinase Inhibitors
  • Pyridines
  • Quinolizines
  • RS 79948-197
  • Receptors, Adrenergic, alpha-2
  • L 657743
  • Y 27632
  • Tetrodotoxin
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Protein Serine-Threonine Kinases
  • rho-Associated Kinases
  • Clonidine
  • fasudil