Thromboxane A2-Driven Vascular Hyperreactivity in Cadmium-Induced Hypertension: Role of Oxidative Stress and Therapeutic Implications.

Background/

Objectives

Environmental factors, including heavy metals such as cadmium, are increasingly recognized as important contributors to hypertension beyond traditional risk factors. To date, the role of angiotensin and alpha-adrenergic receptors in hypertension induced by cadmium exposure has been explored. However, the involvement of thromboxane A2 receptors in vascular hyperreactivity and hypertension in rats with chronic cadmium administration is unknown.

Methods

This study aimed to evaluate changes in vascular reactivity due to the action of thromboxane A2 in isolated aortas from hypertension induced by chronic administration of cadmium (HICAD) rats and whether this effect is associated with changes in the redox balance. Aortas were homogenized in phosphate buffer to assess oxidative stress and vascular reactivity. MDA, 4-HDAs, GPx, and GR were quantified spectrophotometrically. Aortic rings were used for vasodilator and vasoconstrictor responses, evaluating NADPH oxidase involvement using apocynin.

Results

We found that in aortas from HICAD rats there was: (1) a significant increase in malondialdehyde and 4-hydroxyalkenals (2 to 4-fold), as well as a significant reduction in glutathione reductase (~50%), and (2) a significant 35% increase in the vasoconstrictor response to U46619 (thromboxane A2 analogue), but no significant changes (~2%) when incubated with an NADPH oxidase inhibitor.

Conclusions

The increase in the vasoconstrictor response to thromboxane A2 can be measured by the increase in oxidative stress and the involvement of NADPH oxidase.