Effects of Cadmium in Vitro on Contractile and Relaxant Responses of Isolated Rat Aortas

Objective：Cadmium is known to affect the vascular tone of isolated blood vessels in vitro and the arterial pressure of rats in vivo. However, the mechanisms of cadmium actions on the vascular system have not been clarified. To elucidate the actions of cadmium on vascular tonus, effects of cadmium on vasocontractile and vasorelaxant responses in vitro were investigated using aortic strips isolated from rats. Methods: Aortic strips isolated from male Wistar rats were incubated with CdCl2 (10 μM) for 24 hr, washed with fresh CdCl2-free medium, and then used for measurement of isometric tension and Western blot analysis of eNOS (endothelial nitric oxide synthase) and iNOS (inducible nitric oxide synthase). Results: In the aortas pretreated with cadmium in vitro, the contractile response to phenylephrine was significantly higher than that in the control aortic strips pretreated with a vehicle. The sodium nitroprusside-induced relaxing response was significantly higher in the aortic strips pretreated with cadmium for 24 hr, compared with that in the control pretreated with a vehicle. The isoproterenolinduced relaxing response was also significantly higher in the cadmium-accumulated aortic strips. In vitro cadmium treatment slightly but not significantly increased the acetylcholine-induced relaxation of the aortic strips. Cadmium treatment induced expression of iNOS and significantly increased expression of eNOS in the aortic strips, while it did not affect expression of β-actin. Conclusions: Cadmium treatment in vitro augmented the α1 adreaoceptor-mediated contractile response, even though eNOS and iNOS were upregulated by cadmium treatment. NO-induced and β-adrenoceptor-mediated relaxing responses were also augmented by cadmium treatment. These results suggest that both vasocontractile and vasorelaxing responses are augmented in cadmiumaccumulated aortas.