Abstract

Objectives: Use of the radial artery (RA) as a bypass conduit will depend upon its long term patency which is thought to be inhibited by an increased vasoconstrictor response. Glibenclamide (GLIB) is used in the treatment of non-insulin dependent diabetes mellitus (NIDDM). GLIB has also been shown to inhibit prostanoid induced vasoconstriction. We hypothesised that human RA and internal thoracic artery (ITA) should differ in this response if the thicker media of the RA is important in vasoconstriction. We tested the effect of GLIB on vasoconstriction mediated by thromboxane A2 mimetic U46619, the alpha 1 receptor agounist L-phenylephrine and potassium chloride.

Methods: Human RA and ITA placed in ice cold modified Krebs-Henseleit solution, mounted as 3 mm sections in organ bath were aerated in 95% CO₂/5% O₂ at 37°C whilst connected to strain gauge transducer. Each vessel was equiliberated at 3 g tension for 1 hour before assay (1 hr for ITA, 2 hr for RA).

Results: Log concentration-response curves were constructed from the tension developed in response to U46619 and L-phenylephrine. Preincubation of both LIMA (n = 4) and RA (n = 4) vessels with GLIB (10.5 and 5 × 10.5 M) caused the concentration-response curve to both agents to shift in parallel fashion to the right. In addition, concentration dependent relaxation of U46619 preconstricted LIMA and RA vessels was observed in the presence of GLIB, with calculated EC₅₀ values of 4.85 × 10^-5 M for LIMA (n = 4) and 1 × 10^-4 M for RA (n = 4). High concentration of GLIB also relaxed LIMA vessels which had been preconstricted with 70 mM KCL. Relaxation of GLIB was independent of an intact endothelium.

Conclusions: GLIB has a relaxant effect on human RA and ITA. This has important clinical implications for use of RA as a conduit and for NIDDM patients who traditionally are not thought suitable for arterial revascularisation. In addition, it is likely that these effects are due to some mechanism distinct from its effect on KATP channels.