Effects of cromakalim and glibenclamide on arteriolar and venular diameters and macromolecular leakage in the microcirculation during ischemia/reperfusion.
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.
Simões
Claudia
C
Laboratório de Pesquisas em Microcirculação, Universidade do Estado do Rio de Janeiro, Rio de Janeiro RJ, Brazil.
Svensjö
Erik
E
Bouskela
Eliete
E
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002199:Capillary Permeability / Q000187:drug effects*; D002610:Cheek / Q000098:blood supply; D006224:Cricetinae; D019806:Cromakalim / Q000494:pharmacology*; D003911:Dextrans; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D005905:Glyburide / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology; D008208:Lymphatic System / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008647:Mesocricetus; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists / Q000378:metabolism; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology; D014665:Vasodilator Agents / Q000494:pharmacology*
D003911:Dextrans; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014665:Vasodilator Agents; C015219:fluorescein isothiocyanate dextran; D019806:Cromakalim; D006632:Histamine; D000255:Adenosine Triphosphate; D016650:Fluorescein-5-isothiocyanate; D005905:Glyburide