Inhibitory effects of daunorubicin on endothelium-dependent vasorelaxing response to acetylcholine of rat aorta.
The effect of daunorubicin on the endothelium-dependent vasorelaxing response to acetylcholine was investigated using rat isolated aorta and compared with the effect of aclarubicin. Treatment of aortic strips with daunorubicin (20 microM) significantly attenuated the relaxing response to acetylcholine in the absence of tetraethylammonium, but not in its presence. Pretreatment with daunorubicin at a higher concentration (50 microM) or with aclarubicin (20 microM) strongly attenuated the relaxing response to acetylcholine; this attenuation was unaffected by the presence of tetraethylammonium. The increase in aortic cGMP in response to acetylcholine was also significantly suppressed by pretreatment with 50 microM daunorubicin or 20 microM aclarubicin, but not by treatment with 20 microM daunorubicin. The inhibitory effect of 20 microM aclarubicin on the acetylcholine-induced responses was stronger than that of 50 microM daunorubicin. Even in strips pretreated with both 50 microM daunorubicin and 20 microM aclarubicin, relaxation induced by 0.1 microM sodium nitroprusside was retained. These results suggest that daunorubicin at 20 microM inhibits the endothelium-dependent vasorelaxing response to acetylcholine via a mechanism other than the nitric oxide-mediated pathway, whilst at 50 microM, it inhibits the nitric oxide-mediated vasorelaxation.
Wakabayashi
I
I
Department of Hygiene, Hyogo College of Medicine, Japan.
Hatake
K
K
Yoshimoto
S
S
Sakamoto
K
K
D000109:Acetylcholine / Q000494:pharmacology*; D015250:Aclarubicin / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D003630:Daunorubicin / Q000494:pharmacology*; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D026902:Potassium Channel Blockers; D051381:Rats; D017208:Rats, Wistar; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D026902:Potassium Channel Blockers; D013757:Tetraethylammonium Compounds; D010656:Phenylephrine; D019789:Tetraethylammonium; D015250:Aclarubicin; D006152:Cyclic GMP; D000109:Acetylcholine; D003630:Daunorubicin