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Perfusion-time dependent enhancements of guanabenz- and KCl-induced vasoconstrictions in isolated and perfused dog pulmonary veins

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Summary

The responses of the isolated canine pulmonary vein to guanabenz and to potassium chloride (KCl) were examined by means of the cannula-inserting method. The vessel was perfused by Krebs-Ringer bicarbonate solution at a constant flow rate at 37°C. In the early stage (within 2–3 hours of the perfusion period), guanabenz induced a dose-dependent vasoconstriction, whereas high doses of KCl caused, at most, a slight vasoconstriction. At the late stage (within 8–11 hours of the perfusion period), the dose-response curve for guanabenz was shifted to the left and the maximum response became approximately 3-fold larger than that in the early stage. Vasoconstriction in response to KCl was observed in 8 out of 11 preparations (73%) in the late stage. In both early and late stages, guanabenz-induced responses were similarly antagonized by DG-5128 (a selective α2-adrenoceptor antagonist) but not by bunazosin (a selective α1-adrenoceptor antagonist). Diltiazem caused an inhibition of guanabenz-induced constrictions, particularly in the late stage. KCl-induced vasoconstriction was not affected by bunazosin or DG-5128, but was markedly suppressed by diltiazem. In preparations in which the endothelium was removed by intraluminal treatment with saponin, the changes in guanabenz- and KCl-induced responses, which were dependent on the perfusion time, were not modified in either stage.

Our results suggest that α2-adrenoceptor-mediated vasoconstriction is enhanced in a perfusion-time-dependent manner in the isolated and perfused canine pulmonary vein. These enhanced responses mediated by latent α2-adrenoceptors are dependent on the influx of extracellular calcium ions. Because the removal of endothelial cells by saponin did not affect the time-dependent enhancement of the response to guanabenz, the removal of endothelial cells by prolonged perfusion may play little part in the time-dependent enhancement of the α2-adrenoceptor-mediated response.

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Authors and Affiliations

  1. Department of Pharmacology, Shinshu University School of Medicine, 390, Matsumoto, Japan

    Masayuki Haniuda &  Shigetoshi Chiba M.D.

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  1. Masayuki Haniuda
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  2. Shigetoshi Chiba M.D.
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Haniuda, M., Chiba, S. Perfusion-time dependent enhancements of guanabenz- and KCl-induced vasoconstrictions in isolated and perfused dog pulmonary veins. Heart Vessels 5, 212–218 (1990). https://doi.org/10.1007/BF02058692

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