We studied changes in arteriolar and venular diameters and macromolecular leakage altered by
ischemia/reperfusion (I/R) and topically applied
histamine after I/R and how these changes were modulated by
cromakalim (
KATP-channel opener) and
glibenclamide (
KATP-channel blocker). Golden hamsters were prepared for intravital microscopy of the cheek pouch.
Ischemia was induced by an inflatable
silicon rubber cuff mounted around the neck of the cheek pouch prepared for intravital microscopy. Saline,
histamine,
cromakalim, and
glibenclamide were applied in the superfusion
solution.
FITC-dextran was injected i.v. 30 min before initiation of
ischemia as a marker of macromolecular leakage.
Cromakalim 10(-6) M, but not 10(-8) M, caused arteriolar dilation in ischemic and normal (nonischemic) preparations, and
glibenclamide, 10 -10) M and 10(-8) M, had no effects on vessel diameters. Application of
cromakalim 10(-6) M increased arteriolar diameter (+54%) and macromolecular leakage in normal and nonischemic cheek pouches and had an additive effect on macromolecular leakage in ischemic (I/R) preparations but had no effect on
histamine-induced increase in macromolecular leakage.
Glibenclamide, 10(-10) M and 10(-8) M, inhibited I/R-induced but not
histamine-induced increases in macromolecular leakage. We concluded that
cromakalim may increase macromolecular leakage. This effect is additive to I/R-induced leakage suggesting that stimulation of
KATP-channels could take part in the regulation of macromolecular leakage in postcapillary venules. The KATP-blocker
glibenclamide inhibited I/R-induced but not
histamine-induced macromolecular leakage at concentrations that had no constricting effect on arterioles, and therefore, it cannot be excluded that
glibenclamide reduced plasma leakage by some unknown mechanism.