Cadmium exposure induces vascular injury due to endothelial oxidative stress: the role of local angiotensin II and COX-2

Abstract

Cadmium is an environmental pollutant that is closely linked with cardiovascular diseases, such as atherosclerosis and hypertension. Moreover, cadmium can induce an increase in oxidative stress. One of the main sites affected by oxidative stress is the aorta, which consequently develops atherosclerosis. However, there are few reports demonstrating aortic effects induced by small concentrations of cadmium that are similar to those found in the blood resulting from occupational exposure. Furthermore, several studies have reported on chronic cadmium exposure, and the results of these studies may have been influenced by the secondary effects induced by this metal, such as hypertension. Therefore, we investigated the effects of acute cadmium exposure on the vascular reactivity to phenylephrine of aortic rings isolated from male Wistar rats. Cadmium increased phenylephrine reactivity without changing the vasorelaxation induced by acetylcholine and sodium nitroprusside. Endothelial damage or incubation with L-NAME shifted the phenylephrine concentration-response curves leftward in arteries incubated with or without cadmium, but the curves were shifted to a lesser degree after cadmium incubation. Enalapril, losartan, the nonselective COX inhibitor indomethacin, the TXA(2) synthase inhibitor furegrelate, the selective COX-2 inhibitor NS 398, the TP receptor antagonist SQ 29.548, the EP1 receptor antagonist SC 19.220, superoxide dismutase, and the NADPH oxidase inhibitor apocynin partially reverted the cadmium-induced effects on the reactivity to phenylephrine. Cadmium exposure increased vasoconstrictor activity by reducing NO bioavailability owing to the increased production of ROS by NADPH oxidase. The results of the tested cadmium concentration, which is below the reference values, suggest that acute cadmium exposure may induce vascular injury through endothelial oxidative stress. These data contribute to the evidence indicating that cadmium is a high risk to public health.

Clinically Relevant Doses of Candesartan Inhibit Growth of Prostate Tumor Xenografts In Vivo through Modulation of Tumor Angiogenesis

“…In this context, the observed antiproliferative effects of ARBs are basically a reflection of AT1-mediated signaling in cancer cells. This approach does not take into account the possible role of locally produced AngII, which has been demonstrated to be of major importance in other cell types (Reid et al, 2011;Angeli et al, 2013;Lu et al, 2013). In addition, this approach also ignores the possibility of ARBinduced AngII-independent effects which have been demonstrated in other cell types (Alhusban et al, 2013).…”

“…Another important consideration in investigating the effects of ARBs is the concomitant treatment with exogenous AngII (Uemura et al, 2003;Kosaka et al, 2007;Chen et al, 2013), which only blunted AngII-mediated effects. This paradigm ignores AngII-independent effects of candesartan as well as the role of locally produced AngII, which has been well characterized in a variety of tissues and cell types (Reid et al, 2011;Angeli et al, 2013;Lu et al, 2013). Recently, candesartan was shown to be proangiogenic in cerebral microvascular endothelial cells via activation of the angiotensin II type 2 (AT2) receptor (Alhusban et al, 2013).…”

Environmental Endocrine Disruption of Energy Metabolism and Cardiovascular Risk

“…TCDD and other PCB congeners have also been shown to up-regulate MCP-1 expression in other tissues; however, whether these effects are also observed in the vascular tissue is incompletely known [128,129]. Similarly, endothelial dysfunction and inflammation have been shown in animal models of exposure to cadmium [130] and PCBs [126,131]. Endothelial dysfunction, in turn, is known to promote the progression of inflammatory vascular diseases, including atherosclerosis [132].…”

Heavy metals contamination in lipsticks and their associated health risks to lipstick consumers

“…For people who are extremely sensitive to chromium, allergic reactions consisting of severe redness and swelling of the skin have been observed (Gondal et al, 2010). Prolonged exposure to cadmium is closely linked with cardiovascular diseases, such as atherosclerosis and hypertension (Angeli et al, 2013). Other than the non-carcinogenic chronic health risks, exposure to heavy metals might also cause carcinogenic health risks to lipstick consumers.…”