Impairment of endothelium-dependent vasorelaxation in cadmium-hypertensive rats

Abstract

Abnormalities in the production and/or release of relaxing factors from the endothelium have been implicated in the development of hypertension in several animal models. Endothelium-dependent relaxation has been reported to be impaired in thoracic aorta in experimentally induced and genetically hypertensive rats. Present study has extented these observations to thoracic aorta of cadmium-hypertensive rats. The possible role of alterations in oxidant status was also studied. Hypertension was induced by the intraperitoneal administration of 1 mg/kg/day cadmium for 15 days. Mechanical responses produced by acetylcholine (ACh, 10(-9)-10(-4) M) and sodium nitroprusside (SNP, 10(-10)-10(-5) M) were studied on phenylephrine-precontracted thoracic aorta rings from control and cadmium-hypertensive rats. Serum nitric oxide (NO) and aortic malondialdehyde (MDA) levels were measured. ACh-induced relaxation was attenuated in aorta from cadmium-hypertensive rats, whereas relaxation responses to SNP did not differ significantly between the groups. Exposure of aortic rings to N(G)-nitro-L-arginine methyl ester (L-NAME, 10(-4) M) resulted in a significantly greater inhibition of relaxation response to ACh in aortic rings of cadmium-hypertensive rats as compared with control rats. Incubation with L-arginine (L-Arg, 10(-3) M) caused a similar reversal of the inhibition of ACh-induced relaxation by L-NAME in both groups. Serum NO levels were decreased and aortic MDA levels were increased in cadmium-treated rats as compared with control rats. However, the differences between the groups did not reach a statistical significance. These findings suggested that the reduction in endothelium-dependent relaxation may play a role in cadmium-induced hypertension as it was in many other hypertension models.

Cadmium Exposure and Incident Cardiovascular Disease

“…Our results are supported by experimental evidence showing roles of cadmium in oxidative stress, 47 endothelial dysfunction, 10,48,49 atherosclerosis formation, 10,50 hypertension 51,52 and kidney disease. 53 Cadmium-related vascular damage could be partly promoted by dysfunctional metallothionein production in endothelial cells.…”

Cadmium Exposure and Incident Peripheral Arterial Disease

“…The associations between cadmium and PAD observed in SHS are consistent with experimental evidence supporting a variety of potential mechanisms for cadmium as an atherogenic factor, including promoting the formation of reactive oxygen species, 8 interfering with antioxidative stress responses, 8,53 promoting hypertension 54,55 and kidney disease, 56 and causing endothelial dysfunction and damage. [4][5][6]57 Cadmium could also act through epigenetic 58 and endocrine disruption [59][60][61] pathways.…”

Cadmium and hypertension in exposed workers: A meta-analysis

“…More recently, other authors have demonstrated the influence of cadmium on kidney tissues resulting in the decrease of CYP4A11 and PPARs (peroxisome proliferator-activated receptors), with possible production of hypertension, sodium retention, glucose intolerance, dyslipidemia, and zinc depletion [54]. Other studies have shown that cadmium can cause a loss of molecules with vasodilating functions, such as nitric oxide [55], and it can also increase the effect of norepinephrine [56]. In conclusion, some other authors have demonstrated a cadmium-induced endothelial alteration, which would be mediated by an alteration in the functionality of the M1 acetylcholine receptors [57].…”