Xanthine oxidase activity associated with arterial blood pressure in spontaneously hypertensive rats

Hidekazu Suzuki, Frank A. Delano, Dale A. Parks, Neema Jamshidi, D. Neil Granger, Hiromasa Ishii, Makoto Suematsu, Benjamin W. Zweifach, Geert W. Schmid-Schönbein

Research output: Contribution to journalArticle

206 Citations (Scopus)

Abstract

Recent evidences in vivo indicates that spontaneously hypertensive rats (SHR) exhibit an increase in oxyradical production in and around microvascular endothelium. This study is aimed to examine whether xanthine oxidase plays a role in overproduction of oxidants and thereby may contribute to hypertensive states as a consequence of the increasing microvascular tone. The xanthine oxidase activity in SHR was inhibited by dietary supplement of tungsten (0.7 g/kg) that depletes molybdenum as a cofactor for the enzyme activity as well as by administration of (-)BOF4272 [(-)-8-(3-methoxy-4- phenylsulfinylphenyl)pyrazolo(1,5-α)-1,3,5-triazine-4-monohydrate], a synthetic inhibitor of the enzyme. The characteristic elevation of mean arterial pressure in SHR was normalized by the tungsten diet, whereas Wistar Koto (WKY) rats displayed no significant alteration in the pressure. Multifunctional intravital videomicroscopy in mesentery microvessels with hydroethidine, and oxidant-sensitive fluoro-probe, showed that SHR endothelium exhibited overproduction of oxyradicals that coincided with the elevated arteriolar tone as compared with WKY rats. The tungsten diet significantly repressed these changes toward the levels observed in WKY rats. The activity of oxyradical-producing form of xanthine oxidase in the mesenteric tissue of SHR was ≃3-fold greater than that of WKY rats, and pretreatment with the tungsten diet eliminated detectable levels of the enzyme activity. The inhibitory effects of the tungsten diet on the increasing blood pressure and arteriolar tone in SHR were also reproducible by administration of (-)BOF4272. These results suggest that xanthine oxidase accounts for a putative source of oxyradical generation that is associated with an increasing arteriolar tone in this form of hypertension.

Original languageEnglish
Pages (from-to)4754-4759
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number8
DOIs
Publication statusPublished - 1998 Apr 14
Externally publishedYes

Fingerprint

Xanthine Oxidase
Inbred SHR Rats
Tungsten
Arterial Pressure
Inbred WKY Rats
Diet
Oxidants
Endothelium
Video Microscopy
Triazines
Mesentery
Molybdenum
Coenzymes
Enzyme Inhibitors
Dietary Supplements
Microvessels
Blood Pressure
Hypertension
Pressure
Enzymes

Keywords

  • Endothelium
  • Microcirculation
  • Tungsten
  • Xanthine dehydrogenase

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Xanthine oxidase activity associated with arterial blood pressure in spontaneously hypertensive rats. / Suzuki, Hidekazu; Delano, Frank A.; Parks, Dale A.; Jamshidi, Neema; Granger, D. Neil; Ishii, Hiromasa; Suematsu, Makoto; Zweifach, Benjamin W.; Schmid-Schönbein, Geert W.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 8, 14.04.1998, p. 4754-4759.

Research output: Contribution to journalArticle

Suzuki, H, Delano, FA, Parks, DA, Jamshidi, N, Granger, DN, Ishii, H, Suematsu, M, Zweifach, BW & Schmid-Schönbein, GW 1998, 'Xanthine oxidase activity associated with arterial blood pressure in spontaneously hypertensive rats', Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 8, pp. 4754-4759. https://doi.org/10.1073/pnas.95.8.4754
Suzuki, Hidekazu ; Delano, Frank A. ; Parks, Dale A. ; Jamshidi, Neema ; Granger, D. Neil ; Ishii, Hiromasa ; Suematsu, Makoto ; Zweifach, Benjamin W. ; Schmid-Schönbein, Geert W. / Xanthine oxidase activity associated with arterial blood pressure in spontaneously hypertensive rats. In: Proceedings of the National Academy of Sciences of the United States of America. 1998 ; Vol. 95, No. 8. pp. 4754-4759.
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