Renal xanthine oxidoreductase activity during development of hypertension in spontaneously hypertensive rats.
BACKGROUND
Hyperuricaemia and reactive oxygen species have recently been associated with essential hypertension. Xanthine oxidoreductase (XOR) produces urate and, in its oxidase isoform, reactive oxygen species also. Our previous studies indicated that hypertension-prone rat strains have greater renal XOR activity than their normotensive counterparts, and that dietary sodium modifies renal XOR activity.


OBJECTIVE
To clarify whether renal XOR induction precedes or follows the development of hypertension.


METHODS
Five-week-old spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats were kept for 3-8 weeks on low sodium (0.3% salt w/w) or high sodium (6.0% salt w/w) intakes, with or without allopurinol, an inhibitor of XOR, to study the possible pathogenetic role of XOR in hypertension. Systolic blood pressure (SBP), renal XOR activity and mRNA expression were measured.


RESULTS
Regardless of sodium intake, renal XOR activity increased twofold during growth in SHRs, but not in WKY rats. SBP increased from 122 +/- 4 to 241 +/- 13 mmHg in SHRs kept on the high-sodium diet and to 204 +/- 11 mmHg in those on the low-sodium diet. At the end of the experiment, renal XOR activity correlated with SBP in SHRs. Allopurinol prevented hypertension-induced left ventricular and renal hypertrophy in SHRs, but had negligible effect on blood pressure.


CONCLUSIONS
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.
Laakso
Juha T
JT
Institute of Biomedicine, Pharmacology, University of Helsinki, Finland. juha.laakso@helsinki.fi
Teräväinen
Terttu-Liisa
TL
Martelin
Eeva
E
Vaskonen
Timo
T
Lapatto
Risto
R
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006977:Hypertension, Renal / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000201:enzymology* / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D014968:Xanthine Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D004791:Enzyme Inhibitors; D017673:Sodium Chloride, Dietary; D000493:Allopurinol; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase