Role of adenosine-triphosphate-sensitive potassium channels in the mechanical responses of agonist-stimulated isolated porcine coronary arteries.

The aim of this study was to provide evidence supporting the hypothesis that the reactivity of the vascular smooth muscle (VSM) cell is controlled at the cell membrane level by adenosine triphosphate (ATP)-sensitive (K ATP ) K channels, acting as signal amplifying modulators of the function of L-type voltage operated Ca channels. K ATP channels, detected in numerous parts of the vascular tree, are targets for extracellular ATP or adenosine, which stimulate A 2 receptors mediating relaxation. To test the hypothesis of a putative role for K AT P channels switching between vasoconstricting and vasodilating mechanisms, changes in contractile reactivity were measured in helical strips of epicardial porcine coronary artery preparations in response to various vasoconstrictor and vasodilator substances or combination of these. The data show that the tonic component of the biphasic contractions induced by several agonists (acetylcholine, histamine, serotonin), as well as the contractions induced by F- ions (2 mmol/l), which activate G proteins downstream of the receptors could be inhibited by both adenine nucleotides and by cromakalim, known as openers of K ATP channels. The EC 50 values for the dose-response curves established for the inhibition of histamine-induced contractions by adenosine were nearly identical to those obtained for the relaxations of fluoride-induced contractions by cromakalim: resp. 0.556 ± 0.081 and 0.590 ± 0.052 μmol/l (n = 6). Contractions induced by BAY k 8644 (20 nmol/l), by tetraethylammonium (5 mmol/l) or by β-methyldigoxin (1 μmol/l) were also strongly inhibited by 1 μmol/l cromakalim. From the results obtained in this study, it may be concluded that K ATP channels could possibly play an integrative role in the signal transduction mechanism in VSM in that they act as common effectors for both vasoconstrictor and vasodilator agonists.