Alpha 2-adrenergic blockade prevents hyperglycemia and hepatic glutathione depletion in nickel-injected rats.

To study the involvement of the adrenergic system in nickel-induced hyperglycemia and hepatic glutathione depletion in rats, several adrenergic antagonists (phentolamine, prazosin, yohimbine, and propranolol) were administered in a single ip injection before acute nickel treatment (ip injection). Moreover, the effects of nickel on adrenalectomized rats were investigated. Hyperglycemia was suppressed by either alpha-antagonist phentolamine or alpha 2-antagonist yohimbine. Such blockade coincided with the prevention of the hypoinsulinemic response to nickel, which occurred simultaneously to hyperglycemia. Nickel-induced hyperglucagonemia remained almost unaltered by pretreatment with adrenergic antagonists. In adrenalectomized animals treated with nickel, hyperglycemia was attenuated, whereas hypoinsulinemia still persisted. Therefore, catecholamines seemed to participate in nickel-induced hyperglycemia, directly, i.e., stimulating glucose output from liver, or by modulating insulin secretion throughout alpha 2-adrenoreceptor stimulation in pancreatic islets. Hepatic glutathione depletion caused by nickel was prevented by either alpha 1-antagonist prazosin or alpha 2-antagonist yohimbine. Interestingly, adrenalectomy did not alter the drop in hepatic GSH induced by nickel treatment. Overall results suggest that the effects observed after acute nickel exposure were caused by a combined action of catecholamines released from the adrenal glands and those released at the efferent nerves. Such events have been found to be mediated by alpha 2-adrenergic receptors.