Flunarizine and α-adrenergic responses in isolated canine saphenous veins

Abstract

1. Experiments were designed to determine how flunarizine affects contractions of cutaneous veins to α-adrenergic activation. 2. Rings of canine saphenous vein were mounted at optimal length for isometric tension recording in organ chambers filled with physiological salt solution. 3. At concentrations higher than those needed to inhibit KCl-induced contractions, flunarizine inhibited the contractile responses evoked by α2-adrenergic agonists (B-HT 920, xylazine), partial (St-587) and full (cirazoline, phenylephrine) α1-adrenergic agonists and the combined α1-/α2-adrenergic agonist, norepinephrine. 4. The inhibitory effect of flunarizine against α2-adrenergic responses was similar to that produced by other calcium-antagonists and results presumably from inhibition of the influx of extracellular calcium. 5. The inhibitory effect of flunarizine against α1-adrenergic responses was greater than expected and appears to result from competitive antagonism of α1-adrenoceptors (pA2 = 5.79). 6. Therefore, flunarizine can decrease adrenergic contractile responses by depressing the influx of extracellular calcium and by blocking postjunctional α1-adrenoceptors.