Chronic inhibition of xanthine oxidase activity lowers arterial blood pressure in spontaneously hypertensive rats

H. Suzuki, D. N. Granger, S. Laroux, N. Jumshidi, D. Katz, B. W. Zweifach, G. W. Schmid-Schönbein

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Recent in vivo evidence indicates that spontaneously hypertensive rats (SHR) have an elevated level of oxygen free radical production along mesenteric microvascular wall, which can he inhibited by xanthine oxidasc (XO) antagonists. This study was designed to investigate the effect of chronic XO activity inhibition on arterial blood pressure (HP) and microvascular oxidalive slress in SHR. The SHR and its normotensive control, the Wistar Kyoto rat (WKY) were fed for 2 weeks with cither normal chow or tungsten-supplemented (Tg) diet for mactivation of XO. After Tg diet, BP in conscious WKY showed no significant shift, while the elevated BP in SHR was significantly reduced. Under general anesthesia, the mesenteric mierocirculation was observed and arteriolar diameters were recorded. The mesentery was superfused with hydroethidine (HE) to detect intracellular oxygen radical production . Papaverine was topically applied to determine maximum diameter from which arteriolar (one was computed. The elevated level of HE conversion by oxygen free radicals in SHR after Tg diet was significantly reduced down to levels of WKY. The level of HE oxidation in WKY was not affected by the TO diet. The elevated arferiolar tone characteristic of SHR was significantly decreased after Tg diet. These results suggest a role for free radical production by XO of vascular eiidothelium in the pathogenesis of the SHR. Supported by HL-10KHI.

Original languageEnglish
Pages (from-to)A630
JournalFASEB Journal
Issue number3
Publication statusPublished - 1996
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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