Perfusion-time dependent enhancements of guanabenz- and KCl-induced vasoconstrictions in isolated and perfused dog pulmonary veins.
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)
Haniuda
M
M
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Chiba
S
S
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*
D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D011799:Quinazolines; D011942:Receptors, Adrenergic, alpha; C032368:midaglizole; D011189:Potassium Chloride; C018176:bunazosin; D004110:Diltiazem; D006143:Guanabenz