Cadmium Toxicity on Arterioles Vascular Smooth Muscle Cells of Spontaneously Hypertensive Rats

Benny Washington,Elbert Myles,Charlie Mtshali,Shunta Williams,Patrice Armstrong,John Robinson

doi:10.3390/ijerph2006030040

Abstract

Cadmium (Cd) is frequently used in various industrial applications and is a ubiquitous environmental toxicant, also present in tobacco smoke. An important route of exposure is the circulatory system whereas blood vessels are considered to be main stream organs of Cd toxicity. Our previous results indicate that cadmium chloride (CdCl2) affects mean arterial blood pressure in hypertensive rats. We hypothesized that Cd alters the intracellular calcium transient mechanism, by cadmium-induced stimulation of MAPKs (ERK 1 & 2) which is mediated partially through calcium-dependent PKC mechanism. To investigate this hypothesis, we exposed primary cultures of vascular smooth muscle cells (VSMCs) from wistar kyoto (WKY) and spontaneously hypertensive rats (SHR) to increased concentrations of CdCl2 on cell viability, expression of mitogen-activated protein kinases (MAPKs/ERK 1 & 2), and protein kinase C (PKC) which are activated by Cd in several cell types. The results from these studies indicate that CdCl2 decreased cell viability of both SHR and WKY VSMCs in a concentration dependent-manner. Viability of both cell types decreased 33+/-5.3 (SHR) and 39+/-2.3% (WKY) when exposed to 1 microM CdCl2, whereas, 8 and 16 microM reduced viability by 66+/-3.1 and 62+/-4.5% in SHR cells. CdCl2 increased ERK 1 & 2 in a biphasic manner with maximum increase occurring when cells are exposed to 1 and 4 muM in SHR VSMCs, whereas, a reduction in ERK 1 and 2 is observed when WKY cells are treated with 2 microM. The results also indicate that CdCl2 increased PKC a/Beta in both SHR and WKY VSMCs with a greater increase in expression in SHR VSMCs. In addition, the [Ca2+]i chelator, BAPTA, suppressed the CdCl2 effect, whereas, the PKC inhibitor, GF109203X, reduced the CdCl2 induced-effect on PKC expression. The present studies support the hypothesis that Cd can be a risk factor of hypertension through dysfunction of vascular smooth muscle cells under certain conditions.

Highlights

Cd is frequently used in various industrial activities and is a ubiquitous environmental toxicant, present in tobacco smoke
We have shown that CdCl2 increases blood pressure in both spontaneously hypertensive rats (SHR) and wistar kyoto (WKY) rats and chronic exposure of vascular smooth muscle cells (VSMCs) of rats with CdCl2 leads to apoptosis
We examined the effect of CdCl2 on mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) expression in VSMCs of SHR

Summary

Introduction

Cd is frequently used in various industrial activities and is a ubiquitous environmental toxicant, present in tobacco smoke. Cd exposure via the respiratory system has been studied [1] and it has been reported that Cd causes apoptosis in various cell types in vitro [2]. The mechanism involved in the elevation of blood pressure and the apoptotic effects of CdCl2 has not been determined. The evidence indicates that the mitogen-activated protein kinase (MAPK) cascade is involved in the regulation of cell growth, differentiation, and various cellular stress responses which is mediated through intracellular signal transduction in response to a variety of stimuli [3, 4]. MAPK has been studied in response to other stresses [5,6,7] to gain an understanding of the MAPK signaling mechanisms, in cardiovascular disorders [8, 9]

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Results

Conclusion