Inhibitory Effects of Glibenclamide on the Contraction of Human Arterial Conduits used in Coronary Artery Bypass Surgery

Glibenclamide has been shown to inhibit prostanoid-induced contraction in a number of blood vessel types. In this study, the effects of glibenclamide on the contraction of human peripheral arteries in response to both prostanoid and non-prostanoid agonists were compared and possible mechanisms of action were investigated. Segments of left internal mammary artery (LIMA) and radial artery, taken from patients undergoing coronary artery bypass graft (CABG) surgery, were mounted in organ baths containing physiological saline solution aerated with 95% O2/5% CO2 at 37 degrees C. Contractions were obtained by either the use of a thromboxane analogue (U46619), L-phenylephrine, KCl or CaCl2. The effects of glibenclamide on these contractions were observed and pEC50 values were determined after manipulation of a logistic curve-fitting equation. Concentration-dependent relaxation of U46619-contracted LIMA and radial artery was observed in the presence of glibenclamide, with calculated pEC50 values of 4.2+/-0.17 (n = 7) for LIMA and 3.26+/-0.48 (n = 5) for radial artery. Incubation of both LIMA and radial artery with glibenclamide (50 microM) caused the concentration-response curves for U46619 and L-phenylephrine to shift significantly to the right. Similarly the KCl tension relationship was caused to shift to the right. Finally, glibenclamide (100 microM) also had an inhibitory effect on Ca2+-induced tension in radial artery. These results show that the inhibitory effects of glibenclamide on human peripheral blood vessels are not restricted to prostanoid-induced contractions. Furthermore, evidence has been provided to suggest that these effects might be mediated through an interaction with voltage-sensitive Ca2+ channels.