Deleterious effects of levamisole, a cocaine adulterant, in rabbit aorta

Levamisole Impairs Vascular Function by Blocking α-Adrenergic Receptors and Reducing NO Bioavailability in Rabbit Renal Artery

“…This finding may be related to a threshold point for post-junctional α 1 -AR blockade induced by levamisole. Interestingly, in contrast to our previous study [31], a non-significant reduction in the expression of α 2 -AR was observed, further suggesting that intracellular signalling involved in the sympathetic response to levamisole in rabbit renal arteries may also be influenced by other mechanisms, such as the NA reuptake blockade proposed by Hofmaier et al (13). In this regard, although we did not perform experiments comparing whether levamisole mimics the effect of NA reuptake inhibitors, it is worth noting that the vascular effects of levamisole observed in our EFS experiments could be in line with this idea.…”

“…We showed that levamisole enhanced EFS-induced contraction, similar to observations made with yohimbine, a selective α 2 -AR blocker. These data are consistent with what occurs in other vascular beds, such as the rabbit aorta [31]. However, the highest concentration of levamisole abolished this response.…”

“…To our knowledge, this is the first study to demonstrate that levamisole induces endothelial dysfunction in the renal artery. Although this effect has been previously reported by our group in rabbit aorta [31] and by others in mouse aorta [32], it is well known that the mechanism of vascular adaptation varies from one vascular bed to another [33]. Therefore, the vascular response to a stimulus may be heterogeneous between different vascular beds.…”

“…Our previous study [31] demonstrated that levamisole induces relaxation in aorta rings contracted with NA but not in those contracted with ET-1, U46619 or high-K + . These results suggest that levamisole interferes with the selective mechanisms of vascular adrenergic contraction, either by blocking intracellular signal transduction pathways involved in vascular contraction or even by antagonizing AR [34].…”