Dithiothreitol-induced triphasic response of dog coronary arteries.
Exposure of dog coronary arterial strips to dithiothreitol resulted in a triphasic response which was characterized by an initial rapid, weak contraction (phase A), an intervening slow relaxation (phase B) and finally, a slowly developing intense contraction (phase C). No responses were observed when either oxidized dithiothreitol or threitol were used. No contractions were observed if the extracellular Ca2+ was omitted. Ca2+ channel blockers (nicardipine and diltiazem), a protein kinase inhibitor (1-(5-isoquinolinesulfonyl)-2-methylpiperazine, H-7), and a myosin light chain kinase inhibitor (1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine, ML-9), all suppressed the dithiothreitol-induced responses. The calmodulin antagonists, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) and N-(6-aminohexyl)-1-naphthalenesulfonamide (W-5), however, augmented phase A, and W-7 and chlorpromazine depressed phase C. Prolonged exposure of the arteries to dithiothreitol was essential to elicit phase C. The implications of these data are discussed with respect to the possible mechanisms of dithiothreitol-induced vascular responses.
Fujioka
H
H
Department of Biochemistry, Shiga University of Medical Science, Japan.
Horiike
K
K
Takahashi
M
M
Ishida
T
T
Kinoshita
M
M
Nozaki
M
M
D000818:Animals; D002118:Calcium / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects; D004229:Dithiothreitol / Q000494:pharmacology*; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology; D004896:Erythritol / Q000494:pharmacology; D005260:Female; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D012977:Sodium Nitrite / Q000494:pharmacology; D013402:Sugar Alcohols / Q000494:pharmacology
D013402:Sugar Alcohols; D011189:Potassium Chloride; C003460:threitol; D006632:Histamine; D012977:Sodium Nitrite; D004896:Erythritol; D002118:Calcium; D004229:Dithiothreitol; D009638:Norepinephrine