Relaxation of canine airway smooth muscle by the heparin preservative benzyl alcohol

Abstract

To characterize the actions of heparin and its common preservative benzyl alcohol (BA) on airway smooth muscle functions, we studied the effects of purified heparin, commercial heparin salt solution (HSS) containing heparin and BA, and BA on the contractile responses of canine bronchial segments to various agonists under isometric conditions in vitro. Addition of HSS or the equivalent volume of BA reversibly depressed acetylcholine-induced contraction in a dose-dependent fashion, IC50 values being 5.7 +/- 1.1 (SE) mM of BA, whereas purified heparin had no effect. This depression was not affected by pretreatment of tissues with propranolol, indomethacin or ouabain, or removal of epithelium, and BA at sufficient concentrations to cause muscle relaxation did not alter intracellular adenosine 3',5'-cyclic monophosphate contents. BA also attenuated the contractile responses to electrical field stimulation, histamine, and serotonin, but it was without effect on those to KCl. In addition, the acetylcholine-induced enhancement of hydrolysis of phosphatidylinositol 4,5-biphosphate in the lipid fraction and the resultant production of phosphatidic acid were inhibited in the presence of BA. These results suggest that the heparin preservative BA but not heparin relaxes airway smooth muscle, probably through the decrease in intracellular Ca2+ release by inhibiting agonist-mediated phosphatidylinositol turnover.