Acute effects of glibenclamide on reactive hyperaemia in the lower limbs in humans.
Three episodes of 1 min ischemia in the lower limbs in humans reduced the metabolic debt repayment (expressed as AUC of reactive hyperaemia) following more prolonged ischemia (666.6+/-86.6 vs 500.0+/-33.5 ml/100 ml). The administration of the ATP-dependent K(+) channel blocker glibenclamide was associated with a significant reduction in the AUC of reactive hyperaemia (666.6+/-86.6 vs 563.1+/-76.6 ml/100 ml), and with the removal of the protective effect produced by 3 episodes of 1 min ischemia (563.1+/-76.6 vs 551.8+/-71.3 ml/100 ml). Plasma level of glibenclamide reached the peak value of 1.295+/-0.15 micromol/l 2 h after drug administration, ranging around the 1 micromol/l concentration in the following 3 hours. Our findings produce indirect evidence that, similarly to the ischemic preconditioning of the heart, the protective effects towards ischemia of brief repeated episodes of sub-maximal occlusion in the peripheral circulation of the lower limbs in humans are mediated by ATP-dependent K(+) channels.
Capecchi
P L
PL
Department of Clinical Medicine and Immunologcal Sciences, Section of Immunology, University of Siena, Italy. capecchipl@unisi.it
Guideri
F
F
Colafati
M
M
Acampa
M
M
Cuomo
A
A
Lazzerini
P E
PE
Pasini
F Laghi
FL
D000328:Adult; D019540:Area Under Curve; D005260:Female; D005905:Glyburide / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D006940:Hyperemia / Q000188:drug therapy* / Q000517:prevention & control; D007511:Ischemia; D019194:Ischemic Preconditioning / Q000379:methods; D035002:Lower Extremity / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D026902:Potassium Channel Blockers / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology
D026902:Potassium Channel Blockers; D005905:Glyburide