The effect of glibenclamide on cutaneous laser-Doppler flux.
The K(ATP) channels play a crucial role in regulation of vascular tone in conditions of hypoxia. Whether they contribute to peripheral blood flow regulation in human cutaneous microcirculation during a non-hypoxic state is the matter of conflicting in vivo studies that have used plethysmographic method. Our aim was therefore to elucidate the role of K(ATP) channels in human skin microcirculation in three different conditions that evoke different interplays of vascular mechanisms; during resting conditions, during the postocclusive vasodilatation and in the vasoconstriction response to local cold exposure. The laser-Doppler (LD) skin response was monitored in 12 healthy volunteers on the skin of the fingertips of both hands at rest, after the release of an 8-min digital arteries occlusion, and during local cooling of one hand at 15 degrees C. We compared the direct (at the measuring site) and the indirect (at the contralateral non-cooled hand) LD flux response after intradermal microinjection of saline solution (1 mul) and after a microinjection of the K(ATP) channel blocker glibenclamide (8 muM saturated solution) at the measuring site after obtaining the dose-dependent effect of glibenclamide. The effect of the saline solution was used as a reference value. There was a statistically significant lower resting LD flux after the microinjection of glibenclamide 273.6+/-36 PU when compared to the values obtained after the application of the saline solution 375.8+/-31 PU (paired t-test, p=0.016). Glibenclamide also significantly reduced the relative area under the LD flux curve during the PRH response 14551+/-2508 PU*s vs. 6402+/-1476 PU*s (paired t-test, p=0.01) and increased the principal frequency of postocclusive PRH oscillations 0.0931+/-0.01 Hz vs. 0.1309+/-0.02 Hz (p=0.01). In addition, glibenclamide significantly decreased the LD flux during both the direct and indirect response to local cold exposure when compared to the application of saline solution (paired t-test, p<0.01). Our results support the conjecture that ATP sensitive K(+) channels are importantly involved in blood flow regulation of human skin microcirculation in PRH response, in resting conditions as well as in microvascular local cold response.
Institute of Physiology, School of Medicine, Zaloska 4, 1000 Ljubljana, Slovenia. ksenija.cankar@mf.uni-lj.si
Ksenija
K
Cankar
Martin
M
Strucl
D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects*; D003080:Cold Temperature; D004305:Dose-Response Relationship, Drug; D005260:Female; D005905:Glyburide / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006940:Hyperemia / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D007271:Injections, Intradermal; D054086:KATP Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D008845:Microinjections; D026902:Potassium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply*; D014463:Ultrasonography; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D054086:KATP Channels; D026902:Potassium Channel Blockers; D005905:Glyburide