title: Perfusion-time dependent enhancements of guanabenz- and KCl-induced vasoconstrictions in isolated and perfused dog pulmonary veins.
abstract: 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 degrees 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 alpha 2-adrenoceptor antagonist) but not by bunazosin (a selective alpha 1-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 alpha 2-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 alpha 2-adrenoceptors are dependent on the influx of extracellular calcium ions.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Haniuda
authors.forename: S
authors.initials: S
authors.lastname: Chiba
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004110:Diltiazem / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006143:Guanabenz / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology*; D011667:Pulmonary Veins / Q000187:drug effects / Q000502:physiology*; D011799:Quinazolines / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D011799:Quinazolines; D011942:Receptors, Adrenergic, alpha; C032368:midaglizole; D011189:Potassium Chloride; C018176:bunazosin; D004110:Diltiazem; D006143:Guanabenz