Time-dependent enhancement of xylazine-induced, alpha-2 adrenoceptor-mediated vasoconstriction in isolated and perfused canine pulmonary veins

By using the cannula inserting method, vasoconstrictor responses to norepinephrine (a mixed alpha-1 and alpha-2 adrenoceptor agonist), phenylephrine (a selective alpha-1 adrenoceptor agonist), clonidine and xylazine (selective alpha-2 adrenoceptor agonists) were investigated in the isolated and perfused canine pulmonary vein. The segment of vessels was perfused by Krebs-Ringer bicarbonate solution at a constant flow rate at 37 degrees C. Two hours after setting up the perfusion preparation, norepinephrine and phenylephrine induced dose-dependent increases in perfusion pressure. Xylazine and clonidine, however, did not induce any significant responses at this time. Although the vasoconstrictor responses to norepinephrine and phenylephrine did not change statistically during 11 hr after setting up, xylazine-induced responses were perfusion-time-dependently and significantly enhanced 5, 8 and 11 hr after setting up. On the other hand, clonidine induced no significant vascular responses during 11 hr. Xylazine-induced responses were antagonized by DG-5128 (a selective alpha-2 adrenoceptor antagonist), but not by bunazosin (a selective alpha-1 adrenoceptor antagonist). Furthermore, even in the endothelium-removed preparation by treatment with saponin, the enhancement of xylazine-induced responses were similarly observed in a time-dependent manner. These findings suggest that, in the isolated and perfused canine pulmonary vein, xylazine-induced alpha-2 adrenoceptor-mediated vasoconstrictor response was time-dependently enhanced with the presence and absence of the endothelium. In contrast with xylazine, clonidine did not induce significant vasoconstriction during the experiments. This result suggests that clonidine has little activity at the alpha-2 adrenoceptors which mediate latent xylazine-induced vasoconstriction in the isolated, long-time-perfused canine pulmonary veins.