Increased kidney xanthine oxidoreductase activity in salt-induced experimental hypertension.
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 68+/-8 to 143+/-21 microU/mg protein in the Dahl S (P<0.05) but not in Dahl salt-resistant (Dahl R) rats. On basal and high sodium diets, SHR had higher renal XOR activity (101+/-10 and 134+/-26 microU/mg protein, respectively) than normotensive Wistar-Kyoto rats (55+/-2 and 58+/-6 microU/mg protein, P<0.05). 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.
Laakso
J
J
Institute of Biomedicine, Departments of Medical Chemistry, Pharmacology and Toxicology, University of Helsinki, Finland. juha.laakso@helsinki.fi
Mervaala
E
E
Himberg
J J
JJ
Teräväinen
T L
TL
Karppanen
H
H
Vapaatalo
H
H
Lapatto
R
R
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007668:Kidney / Q000033:anatomy & histology / Q000201:enzymology*; D008297:Male; D009929:Organ Size; D051381:Rats; D020303:Rats, Inbred Dahl; D011918:Rats, Inbred SHR; D012982:Sodium, Dietary / Q000008:administration & dosage*; D014968:Xanthine Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D004791:Enzyme Inhibitors; D012982:Sodium, Dietary; D000493:Allopurinol; D014968:Xanthine Dehydrogenase