Effects of a cardiotonic agent, TA-064, on isolated canine cerebral, coronary, femoral, mesenteric, and renal arteries.

Abstract

We investigated the effects of a newly synthesized cardiotonic agent, TA-064, on helical strips of isolated canine cerebral, coronary, femoral, mesenteric, and renal arteries. TA-064 had no effect on isolated arterial strips under resting tension. When the arterial strips were partially contracted with prostaglandin F2 alpha, TA-064 caused markedly significant concentration-related relaxations in coronary arterial strips. However, the maximum relaxation induced by TA-064 in renal, mesenteric, and femoral arterial strips was only one-third or less of the coronary artery. On the other hand, cerebral arterial strips generated negligible responses to TA-064. Relaxation of renal, mesenteric, and femoral arteries was not potentiated by pretreatment with 10(-5) M phenoxybenzamine. The concentration-response curve for TA-064 in coronary artery was shifted to the right to a similar extent by exposure to 2 X 10(-7) M propranolol and 2 X 10(-7) M metoprolol. On the other hand, relaxation of renal arterial strips was only slightly attenuated by metoprolol but was inhibited by propranolol. Droperidol (3 X 10(-5) M) failed to significantly alter the concentration-response curve for TA-064 in coronary artery. These results indicate that TA-064 causes coronary arterial vasodilatation mediated by beta 1-adrenoceptors. It would further appear that the same mechanism may be responsible for the positive inotropic action of TA-064.