Abstract-Clinical and experimental studies have established an association between high sodium intake and arterial hypertension. The renal mechanisms resulting in impaired sodium excretion in hypertension-prone subjects are not clear. In hypertension-prone rats, high blood pressure results in increased renal mass and hemodynamic changes, both of which may alter renal oxygen distribution. Xanthine oxidoreductase (XOR) oxidizes ATP metabolites hypoxanthine and xanthine to urate. Because XOR is induced by hypoxia, we assessed kidney XOR activity in 2 models of salt-sensitive hypertension, spontaneously hypertensive rats (SHR) and Dahl salt-sensitive (Dahl S) rats. Increasing sodium intake from basal (0.08%) to high (2.56% wt/dry wt in the diet) increased renal XOR activity dose-dependently from 68Ϯ8 to 143Ϯ21 U/mg protein in the Dahl S (PϽ0.05) but not in Dahl salt-resistant (Dahl R) rats. On basal and high sodium diets, SHR had higher renal XOR activity (101Ϯ10 and 134Ϯ26 U/mg protein, respectively) than normotensive Wistar-Kyoto rats (55Ϯ2 and 58Ϯ6 U/mg protein, PϽ0.05). Sodium restriction (0.02% wt/wt) downregulated kidney XOR activity in both Dahl S and R rats by nearly 40%. In SHR, allopurinol treatment totally inhibited renal XOR activity, but neither systolic blood pressure nor renal mass changed. The results suggest that renal XOR induction is a consequence of increased salt intake or the resulting hypertension. However, further studies on renal XOR activity during the development of hypertension are needed to assess the importance of XOR in the pathophysiology of arterial hypertension. (Hypertension. 1998;32:902-906.)Key Words: hypertension, essential Ⅲ xanthine oxidoreductase Ⅲ rats, inbred SHR Ⅲ rats, Dahl Ⅲ hypertrophy Ⅲ sodium Ⅲ allopurinol I n salt-sensitive rats, increasing salt intake results in marked hypertension and left ventricular and renal enlargement within weeks. The genetically related salt-insensitive rats develop these harmful, sodium-induced effects to a much lesser extent.1-3 Kidney transplants derived from normotensive rats have been shown to decrease permanently the systolic blood pressure of an adult salt-sensitive recipient and also abolish the predisposition to hypertension in young animals.4,5 These observations, based on studies on the spontaneously hypertensive rat (SHR) and its normotensive control Wistar-Kyoto rat (WKY) as well as the Dahl saltsensitive (Dahl S) and salt-resistant (Dahl R) rat, indicate the crucial importance of the kidney in the pathogenesis of hypertension. Mechanisms resulting in an impaired excretion of sodium in relation to renal perfusion pressure in saltsensitive rat strains have not been fully worked out.

Renal XOR induction in SHRs does not precede the development of hypertension, but progress concomitantly with an increase in SBP. The results indicate a role for locally synthesized XOR in the development of hypertension-associated end-organ damage, but no major role in the development of hypertension.

Arterial hypertension, nephrotoxicity, and magnesium loss are common side effects of the immunosuppressive agent cyclosporin A (CsA). In the present study, the effects of dietary sodium and magnesium on CsA toxicity were examined in spontaneously hypertensive rats. A 6-week treatment with CsA during a moderately low-sodium diet (Na 0.3%, Mg 0.2% of the dry weight of the chow) raised blood pressure only slightly, without evidence of nephrotoxicity. By contrast, CsA during a high-sodium diet (Na 2.6%) produced a pronounced rise in blood pressure as well as marked nephrotoxicity, comprising decreased creatinine clearance, increased levels of serum creatinine and urea, and increased urinary protein excretion. During the high-sodium diet, CsA decreased myocardial and bone magnesium concentration and increased myocardial and renal calcium concentration. Magnesium supplementation (Mg 0.6%) protected against the CsA-induced hypertension and nephrotoxicity during the high-sodium diet. Magnesium supplementation also completely prevented the CsA-induced myocardial magnesium depletion and calcium accumulation in the heart and kidney during the high-sodium diet. Our findings indicate a detrimental interaction between increased sodium intake and CsA treatment and a marked protection by concomitant oral magnesium supplementation.

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