Involvement of cholinoceptors in cadmium-induced endothelial dysfunction

Abstract

Cadmium (Cd) toxicity was produced in male rats to study the role of cholinoceptors in Cd-induced endothelial dysfunction. The changes in the tension of the aortic rings to constrictor and dilator agonists were compared with those of controls. A Cd-induced significant increase in phenylephrine response was associated with a decrease in basal dilator prostanoid release. In Cd-exposed rings, despite an obvious depression in the acetylcholine (ACh) response, the receptor-independent dilation to the calcium ionophore A23187, which elicits a receptor-independent endothelial relaxation, was slightly elevated (p< 0.01), but the smooth muscle cell response to the NO donor, sodium nitroprusside (SNP) remained unaltered. Cadmium decreased both the maximal response to ACh (10-5M) and its pirenzepine (Prz) sensitive component. The M1 type cholinoceptor-mediated response to ACh decreased in Cd-exposed rings to 10.30 ± 5.00% from 38.40 ± 6.90% (p< 0.001). Cadmium also reduced the share of indomethacin 1.64% to 13.92 ± 2.89% (p< 0.01), which correlated well with the changes in the M1-mediated response (r= 0.991, p < 0.0001). Most of the deleterious effect of Cd appears to Abbreviations: Cd = Cadmium, ACh = Acetylcholine, PG12= Prostacyclin, Indo = Indomethacin, L-NAME = N (G)-nitro-L-arginine methyl ester, EDHF = Endothelium-derived hyperpolarizing factor, Galla = Gallamine, PE = Phenylephrine, Prz = Pirenzepine, Atr = Atropine be restricted to the M1-dependent ACh response. These findings suggest that Cd produces an endothelial dysfunction by impairing the Ml type cholinoceptor mediated response, which seems to be involved in prostanoid release. © 2011, by Walter de Gruyter GmbH & Co. All rights reserved.