This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Laakso, J. Articles by Lapatto, R. Search for Related Content PubMed PubMed Citation Articles by Laakso, J. Articles by Lapatto, R. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ALLOPURINOL Medline Plus Health Information Dietary Sodium

(Hypertension. 1998;32:902-906.)
© 1998 American Heart Association, Inc.

Scientific Contributions

Increased Kidney Xanthine Oxidoreductase Activity in Salt-Induced Experimental Hypertension

Juha Laakso; Eero Mervaala; Jaakko-Juhani Himberg; Terttu-Liisa Teräväinen; Heikki Karppanen; Heikki Vapaatalo; ; Risto Lapatto

From the Institute of Biomedicine, Departments of Medical Chemistry (R.L.) and Pharmacology and Toxicology (J.L., E.M., T.-L.T., H.K., H.V.), University of Helsinki, and the Helsinki University Central Hospital Laboratory Department (J.-J.H.) and Hospital for Children and Adolescents (R.L.), Helsinki, Finland.

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 68±8 to 143±21 µU/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 µU/mg protein, respectively) than normotensive Wistar-Kyoto rats (55±2 and 58±6 µU/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.

Key Words: hypertension, essential • xanthine oxidoreductase • rats, inbred SHR • rats, Dahl • hypertrophy • sodium • allopurinol

This article has been cited by other articles:

				N. Tian, R. S. Moore, W. E. Phillips, L. Lin, S. Braddy, J. S. Pryor, R. L. Stockstill, M. D. Hughson, and R. D. Manning Jr. NADPH oxidase contributes to renal damage and dysfunction in Dahl salt-sensitive hypertension Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2008; 295(6): R1858 - R1865. [Abstract] [Full Text] [PDF]

				A. Boueiz, M. Damarla, and P. M. Hassoun Xanthine oxidoreductase in respiratory and cardiovascular disorders Am J Physiol Lung Cell Mol Physiol, May 1, 2008; 294(5): L830 - L840. [Abstract] [Full Text] [PDF]

				T. M. Paravicini and R. M. Touyz NADPH Oxidases, Reactive Oxygen Species, and Hypertension: Clinical implications and therapeutic possibilities Diabetes Care, February 1, 2008; 31(Supplement_2): S170 - S180. [Abstract] [Full Text] [PDF]

				T. M. Paravicini and R. M. Touyz Redox signaling in hypertension Cardiovasc Res, July 15, 2006; 71(2): 247 - 258. [Abstract] [Full Text] [PDF]

				N. E. Taylor, P. Glocka, M. Liang, and A. W. Cowley Jr NADPH Oxidase in the Renal Medulla Causes Oxidative Stress and Contributes to Salt-Sensitive Hypertension in Dahl S Rats Hypertension, April 1, 2006; 47(4): 692 - 698. [Abstract] [Full Text] [PDF]

				P. Pacher, A. Nivorozhkin, and C. Szabo Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol. Rev., March 1, 2006; 58(1): 87 - 114. [Abstract] [Full Text] [PDF]

				R. Juncos, N. J. Hong, and J. L. Garvin Differential effects of superoxide on luminal and basolateral Na+/H+ exchange in the thick ascending limb Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2006; 290(1): R79 - R83. [Abstract] [Full Text] [PDF]

				N. Tian, K. D. Thrasher, P. D. Gundy, M. D. Hughson, and R. D. Manning Jr Antioxidant Treatment Prevents Renal Damage and Dysfunction and Reduces Arterial Pressure in Salt-Sensitive Hypertension Hypertension, May 1, 2005; 45(5): 934 - 939. [Abstract] [Full Text] [PDF]

				C. E. Berry and J. M. Hare Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications J. Physiol., March 15, 2004; 555(3): 589 - 606. [Abstract] [Full Text] [PDF]

				P. A. Ortiz and J. L. Garvin Superoxide stimulates NaCl absorption by the thick ascending limb Am J Physiol Renal Physiol, November 1, 2002; 283(5): F957 - F962. [Abstract] [Full Text] [PDF]

				A. Tisler, A. Pierratos, J. D'A. Honey, S. B. Bull, L. Rosivall, and A. G. Logan High urinary excretion of uric acid combined with high excretion of calcium links kidney stone disease to familial hypertension Nephrol. Dial. Transplant., February 1, 2002; 17(2): 253 - 259. [Abstract] [Full Text] [PDF]

				E. M. A. Mervaala, Z. J. Cheng, I. Tikkanen, R. Lapatto, K. Nurminen, H. Vapaatalo, D. N. Muller, A. Fiebeler, U. Ganten, D. Ganten, et al. Endothelial Dysfunction and Xanthine Oxidoreductase Activity in Rats With Human Renin and Angiotensinogen Genes Hypertension, February 1, 2001; 37(2): 414 - 418. [Abstract] [Full Text] [PDF]

				A.-P. Zou, N. Li, and A. W. Cowley Jr. Production and Actions of Superoxide in the Renal Medulla Hypertension, February 1, 2001; 37(2): 547 - 553. [Abstract] [Full Text] [PDF]