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 language | English |
|---|---|
| Pages (from-to) | 4754-4759 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 95 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 1998 Apr 14 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Xanthine oxidase activity associated with arterial blood pressure in spontaneously hypertensive rats
AU - Suzuki, Hidekazu
AU - Delano, Frank A.
AU - Parks, Dale A.
AU - Jamshidi, Neema
AU - Granger, D. Neil
AU - Ishii, Hiromasa
AU - Suematsu, Makoto
AU - Zweifach, Benjamin W.
AU - Schmid-Schönbein, Geert W.
PY - 1998/4/14
Y1 - 1998/4/14
N2 - 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.
AB - 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.
KW - Endothelium
KW - Microcirculation
KW - Tungsten
KW - Xanthine dehydrogenase
UR - http://www.scopus.com/inward/record.url?scp=0032516037&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032516037&partnerID=8YFLogxK
U2 - 10.1073/pnas.95.8.4754
DO - 10.1073/pnas.95.8.4754
M3 - Article
VL - 95
SP - 4754
EP - 4759
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 8
ER -