Abstract
Zn-excess intake augmented blood pressure (BP) and reduced renal blood flow (RBF) and inulin clearance. The decline in inulin clearance may be due to a fall in RBF. Treatment with the nitric oxide (NO) synthase inhibitor, L-NAME, further increased BP and markedly decreased RBF in the Zn-excess condition. Inversely, administration of the exogenous superoxide radical scavenger, tempol, significantly decreased BP and substantially increased RBF in the Zn-excess setting. As a result, tempol dramatically restored BP and RBF levels seen in the Zn-excess setting to levels comparable to those observed in the control setting. These observations suggest that both an increment in BP and a decrement in RBF seen in the Zn-excess condition come from a decrement in the action of the vasodilator, NO, via the formation of peroxynitrite based upon the non-enzymatic reaction of NO with increased superoxide radical. Indeed, the activity of the endogenous superoxide radical scavenger, Cu/Zn-superoxide dismutase (SOD), was significantly decreased in the vessel wall of the Zn-excess vs. the control setting. The reduction in the activity of Cu/Zn-SOD in the Zn-excess setting was the result of Cu deficiency secondary to Zn-excess ingestion. With respect to BP, RBF, inulin clearance, L-NAME and tempol treatment and the activity of Cu/Zn-SOD, similar results were observed in the Zn-deficient setting. Thus, inadequate ingestion of Zn leads to the deterioration of BP and renal function through the oxidative stress caused by superoxide radical.
