INHIBITORY EFFECTS OF DAUNORUBICIN ON ENDOTHELIUM-DEPENDENT VASORELAXING RESPONSE TO ACETYLCHOLINE OF RAT AORTA

The effect of daunorubicin on the endothelium-dependent vasorelaxing r esponse to acetylcholine was investigated using rat isolated aorta and compared with the effect of aclarubicin. Treatment of aortic strips w ith daunorubicin (20 mu M) significantly attenuated the relaxing respo nse to acetylcholine in the absence of tetraethylammonium, but not in its presence. Pretreatment with daunorubicin at a higher concentration (50 mu M) or with aclarubicin (20 mu M) strongly attenuated the relax ing response to acetylcholine; this attenuation was unaffected by the presence of tetraethylammonium. The increase in aortic cGMP in respons e to acetylcholine was also significantly suppressed by pretreatment w ith 50 mu M daunorubicin or 20 mu M aclarubicin, but not by treatment with 20 mu M daunorubicin. The inhibitory effect of 20 mu M aclarubici n on the acetylcholine-induced responses was stronger than that of 50 mu M daunorubicin. Even in strips pretreated with both 50 mu M daunoru bicin and 20 mu M aclarubicin, relaxation induced by 0 1 mu M sodium n itroprusside was retained. These results suggest that daunorubicin at 20 mu M inhibits the endothelium-dependent vasorelaxing response to ac etylcholine via a mechanism other than the nitric oxide-mediated pathw ay, whilst at 50 mu M, it inhibits the nitric oxide-mediated vasorelax ation.