Trace elements modify the activity of sodium transporting systems in erythrocyte membrane in patients with essential hypertension–preliminary study

Sir,

It has been reported that deficiency of trace elements, such as copper (Cu) and zinc (Zn), or their imbalance can be associated with an increased risk of hypertension [1,2]. These elements are cofactors of many enzymes, e.g. superoxide dismutase, and they assist in the formation of antioxidative reactions. However, their role in the pathogenesis of hypertension and cardiovascular disease has not yet been fully explained. The pathogenesis of essential hypertension (EH) is associated with increased activity of the Na+/Li+ exchanger, the Na+/H+ exchanger (NHE) and Na+/K+ ATPase [3–5]. Oxidative stress is one of the factors that can influence the activity of these systems [6–8].

The aim of the study was to verify the hypothesis of whether trace elements such as copper and zinc could influence the activity of sodium-transporting systems (STS) and therefore be associated with EH.

The examined group of patients consisted of 15 men aged 39.1±12.2 years with recently diagnosed hypertension. The control group was composed of 11 healthy male volunteers aged 41.1±13.5 years (NS). Further characteristics of the study group and control group are presented in Table 1. NHE activity in erythrocytes was determined according to Orlov et al. [9]. The activity of the transporting systems ATP-Na+/K+; co-Na+/K+/Cl, ex-Na+/Li+, and free Na+ and K+ outflow (Na+, K+-outflow) was determined according to the method of Garay et al. [10] (Table 1). The concentrations of copper and zinc in plasma were assessed using atomic absorption spectrometry (Table 1).


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Table 1. Characteristics of the examined groups of patients

 
In hypertensive patients, the activity of the NHE was positively correlated with the free Na outflow (RS = + 0.539, P<0.05) and with the activity of Na+/K+/Cl co-transporter (RS = +0.606, P<0.02). In the control group, we did not find any correlation between the activities of erythrocyte STS.

In hypertensive patients, negative correlations were found between plasma copper concentration and the activity of Na+/K+/Cl co-transporter and of ex-Na+/Li+ (Figure 1). In the control group, there were no correlations between erythrocyte STS activity and plasma copper concentration. No significant relationships existed between zinc concentration and erythrocyte STS activity in hypertensive and control groups.



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Fig. 1. (A) Correlation between the activity of erythrocyte Na+/Li+ exchanger and plasma copper concentration in patients with hypertension. (B) Correlation between the activity of erythrocyte Na+/K+/Cl co-transporter and plasma copper concentration in patients with hypertension.

 
The specific role of copper in the change of STS kinetics could be the result of two different roles for copper during oxidative stress. First, as copper is a component of superoxide dismutase, in the presence of low plasma copper concentrations, there could be a deficiency of superoxide dismutase co-factor; therefore, oxidative stress indirectly increases, as reflected by the increased STS activity. On the other hand, copper ions are strong oxidants. Copper (I), during reactions with oxygen, produces the superoxide anion radical, and copper (II) as an oxidant takes part in the oxidation of –SH groups of haemoglobin. [11]. We hypothesize that in the presence of high copper concentrations, some functions of cellular membranes are damaged, as reflected by the reduced activity of STS.

In conclusion, the plasma concentration of copper significantly modifies the activity of Na+ transporting systems in erythrocyte membranes.

Karolina Kedzierska1, Joanna Bober2, Kazimierz Ciechanowski1, Edyta Golembiewska1, Ewa Kwiatkowska1, Iwona Nocen2, Grazyna Dutkiewicz1 and Dariusz Chlubek2

1 Department of Nephrology Transplantology and Internal Medicine2 Department of Biochemistry and Chemistry Pomeranian Medical University Szczecin Poland Email: karolina.kedzierska{at}interia.pl

Acknowledgments

This work was supported by a Polish Committee of Scientific Research Grant no 6 P05A 065 20 and Grant no 6 P05A 066 20.

Conflict of interest statement. None declared.

References

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