Mechanisms in inhibitory action of aclarubicin on contractility of rat aorta.
The effects of aclarubicin on vasocontractile response and 45Ca2+ influx were investigated using rat isolated aorta. KCl-induced contractile force in medium containing 2 center dot 5 mM calcium and calcium-induced contractile force in high K+ (60 mM)-depolarized aorta were both markedly attenuated by aclarubicin (70 microM) pretreatment. 45Ca2+ influx stimulated by 60 mM KCl was significantly lower in the aclarubicin (70 microM)-pretreated aorta compared with the control. Aclarubicin pretreatment attenuated phorbol 12, 13-dibutyrate (1 microM)-induced contraction both in the presence and absence of calcium in the medium. Aclarubicin pretreatment also attenuated caffeine (20 mM)-induced transient contraction. These results suggest that aclarubicin attenuates vasoconstriction by inhibiting both Ca2+ entry through the voltage-dependent calcium channel and the intracellular contractile pathway after elevation of intracellular free calcium in vascular smooth muscle, in addition to the known mechanism of inhibition of phosphoinositides hydrolysis.
Wakabayashi
I
I
Department of Hygiene, Hyogo College of Medicine, Nishinomiya, Japan.
Hatake
K
K
Masui
H
H
Sakamoto
K
K
D015250:Aclarubicin / Q000494:pharmacology*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000493:pharmacokinetics; D002132:Calcium Radioisotopes; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000903:Antibiotics, Antineoplastic; D002132:Calcium Radioisotopes; D010716:Phosphatidylinositols; D015240:Phorbol 12,13-Dibutyrate; D002110:Caffeine; D011189:Potassium Chloride; D015250:Aclarubicin; D002118:Calcium