Evaluation of the Vasomodulatory Activity of some Cardiotoxic Drugs

Résumé

The inadequacy of approaches for control of drug-induced cardiotoxicity, suggests the possibility that yet to be explored mechanisms are involved. This study was performed to assess arthemether-lumefanthrine combination (A/Lcomb), 5-fluorouracil (5-Fu) and cisplatin for their vasomodulatory potential as an attempt to identify the possible contribution of such modulation to their adverse effect on the cardiovascular system. This was done using isolated rat aortic ring preparations securely positioned in tissue baths aerated with carbogen (95% carbon dioxide and 5% oxygen). Following tissue equilibration, the direct effect of A/Lcomb, 5-Fu and cisplatin on aortic rings were determined followed by an evaluation of their effect on noradrenaline (3.33 x 10-4 mg/ml) and potassium chloride (4.48 mg/ml) pre-contracted aortic rings. Noradrenaline and potassium chloride pre-contracted aortic rings were significantly relaxed by A/Lcomb. The anti-neoplastic, 5-Fu, significantly increased contractility of aortic rings with or without pre-contraction by noradrenaline or KCl. Cisplatin also significantly increased contractility of noradrenaline pre-contracted tissues. The findings of this study revealed the vasomodulatory action of these drugs, an effect that may contribute to their cardiotoxic potential. A more detailed study to further elucidate the mechanisms by which these vasomodulatory responses are mediated is ongoing.