A possible mechanism of endothelium-dependent relaxation induced by pirarubicin and carbachol in rat isolated aorta.
The mechanism of endothelium-dependent relaxation induced by pirarubicin, (2''R)-4'-O-tetrahydropyranyladriamycin, THP, or carbachol was investigated in the rat isolated aorta. The relaxant effect of THP (1.5 x 10(-6)-4.5 x 10(-5) M) or carbachol (10(-8)-10(-4) M) on the aorta with endothelium was decreased by lowering Ca2+ in the medium. The relaxation induced by THP was not inhibited by pretreatment with verapamil (10(-6)-10(-5) M), and that induced by carbachol was only partially inhibited. However, on replacement of all but 20 mM Na+ with either Li+ or choline, the THP- or carbachol-induced relaxation was inhibited. Furthermore, the relaxing effect of THP or carbachol was inhibited by pretreatment with amiloride (10(-4)-3 x 10(-4) M), with ouabain (10(-4)-10(-3) M), or with K(+)-depletion. These results suggest that the THP- or carbachol-induced relaxation depending on endothelium was affected by modifying the calcium ion concentration, and that a Na(+)-Ca2+ exchange process is involved.
Hirano
S
S
Central Research Laboratories, Mercian Corp., Fujisawa, Japan.
Agata
N
N
Hara
Y
Y
Iguchi
H
H
Shirai
M
M
Tone
H
H
Urakawa
N
N
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002118:Calcium / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology*; D002794:Choline / Q000494:pharmacology; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D007474:Ion Exchange; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000502:physiology; D014700:Verapamil / Q000494:pharmacology
D010042:Ouabain; D000584:Amiloride; D004317:Doxorubicin; D002217:Carbachol; D012964:Sodium; D014700:Verapamil; C027260:pirarubicin; D002794:Choline; D011188:Potassium; D002118:Calcium