title: Cellular mechanisms underlying cutaneous pressure-induced vasodilation: in vivo involvement of potassium channels.
abstract: In the skin of humans and rodents, local pressure induces localized cutaneous vasodilation, which may be protective against pressure-induced microvascular dysfunction and lesion formation. Once activated by the local pressure application, capsaicin-sensitive nerve fibers release neuropeptides that act on the endothelium to synthesize and release nitric oxide (NO) and prostaglandins, leading to the development of the cutaneous pressure-induced vasodilation (PIV). The present study was undertaken to test in vivo the hypothesis that PIV is mediated or modulated by differential activation of K+ channels in anesthetized rats using pharmacological methods. Local pressure was applied at 11.1 Pa/s. Endothelium-independent and -dependent vasodilation were tested using iontophoretic delivery of sodium nitroprusside (SNP) and acetylcholine (ACh), respectively, and was correlated with PIV response. PIV was reduced after systemic administration of tetraethylammonium (a nonspecific K+ channel blocker), iberiotoxin [a specific large-conductance Ca2+-activated K+ (BKCa) channel blocker], and glibenclamide [a specific ATP-sensitive K+ (KATP) channel blocker], whereas PIV was unchanged by apamin (a specific small-conductance Ca2+-activated K+ channel blocker) and 4-aminopyridine (a specific voltage-sensitive K+ channel blocker). The responses to SNP and ACh were reduced by iberiotoxin but were unchanged by glibenclamide. We conclude that the cellular mechanism of PIV in skin involves BKCa and KATP channels. We suggest that the opening of BKCa and KATP channels contributes to the hyperpolarization of vascular smooth muscle cells to produce PIV development mainly via the NO and prostaglandin pathways, respectively.
authors.affiliation: Laboratory of Physiology, UMR Centre National de la Recherche Scientifique 6188, School of Medicine, F-49045 Angers Cedex, France.
authors.forename: Ambroise
authors.initials: A
authors.lastname: Garry
authors.forename: Dominique
authors.initials: D
authors.lastname: Sigaudo-Roussel
authors.forename: Sandra
authors.initials: S
authors.lastname: Merzeau
authors.forename: Odile
authors.initials: O
authors.lastname: Dumont
authors.forename: Jean Louis
authors.initials: JL
authors.lastname: Saumet
authors.forename: Berengere
authors.initials: B
authors.lastname: Fromy
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D007478:Iontophoresis; D051036:Large-Conductance Calcium-Activated Potassium Channels; D040542:Mechanotransduction, Cellular / Q000502:physiology; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000166:cytology; D012879:Skin Physiological Phenomena; D051640:Small-Conductance Calcium-Activated Potassium Channels; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D024642:Potassium Channels, Voltage-Gated; D051640:Small-Conductance Calcium-Activated Potassium Channels; D014665:Vasodilator Agents; D009599:Nitroprusside; D000255:Adenosine Triphosphate; D000109:Acetylcholine