The effect of glibenclamide on acetylcholine and sodium nitroprusside induced vasodilatation in human cutaneous microcirculation

Abstract

K(ATP) channels have an important regulatory role in resting vascular tone and during hypoxia. Their role in endothelium dependent and independent vasodilatation in human skin microcirculation is less known. We monitored the laser-Doppler (LD) response in 14 healthy male volunteers on the skin of the forearm. In the case of endothelium dependent vasodilatation [acetylcholine (ACh) induced], a saline solution (used as control) or a solution of glibenclamide (K(ATP) channel blocker) were randomly injected each into a distinct measurement site on different forearms followed by the iontophoresis of ACh. In the case of endothelium dependent vasodilatation with the inhibition of prostaglandin production, diclofenac (cyclooxygenase inhibitor) or the combination of diclofenac and glibenclamide were randomly injected each into a distinct measurement site on different forearms followed by the iontophoresis of ACh. In the case of endothelium independent vasodilatation [sodium nitroprusside (SNP) induced], a saline solution or glibenclamide were randomly injected each into a distinct measurement site on different forearms, iontophoresis of SNP followed. Glibenclamide alone, diclofenac alone or the combination of glibenclamide and diclofenac reduced the LD flux values during rest and after ACh application (P<0.05). The reduction of LD flux in ACh mediated vasodilatation was greatest when using the combination of glibenclamide and diclofenac. In the case of SNP application, there was also a significantly lower LD flux rise for glibenclamide in comparison with the saline solution (P<0.05). K(ATP) channels play an important role in human cutaneous vasodilatation induced by ACh and SNP.