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Regulation of intracellular xanthine oxidase by endothelial-derived nitric oxide.
Am J Physiol. 1996 Nov; 271(5 Pt 1):L869-74.AJ

Abstract

We have previously shown that nitric oxide (NO) donors, such as nitrosoglutathione, inhibit endothelial cell (EC) xanthine dehydrogenase (XD)/xanthine oxidase (XO) activity. The purpose of this study was to assess whether endothelial-derived NO plays any role in the regulation of intracellular XD/XO. We exposed rat pulmonary microvascular EC to L-arginine (precursor of NO) or inhibitors of nitric oxide synthase (NOS), i.e., NG-nitro-L-arginine methyl esther (L-NAME) and NG-nitro-L-arginine, in conditions of normoxia, hypoxia, and hypoxia followed by reoxygenation. Hypoxia alone caused a 1.9- and a 6.6-fold increase in XO and a 5-fold increase in XO + XD activities after 24 and 48 h of exposure, respectively. The combination of hypoxia and L-NAME (300 microM) treatment amounted at 48 h to a 10- and 7.5-fold increase in XO and XO + XD activities, respectively, compared with normoxic untreated cells. L-NAME also prevented the decline in XD/XO activity that occurred in untreated EC after hypoxia-reoxygenation. On the other hand, treatment with L-arginine caused a dose-dependent decrease in XD/XO activity in hypoxic EC compared with cells provided with L-arginine-free medium. In separate experiments, we assessed the role of L-arginine supplementation on the in vivo regulation of lung XD/XO by exposing male adult Sprague-Dawley rats for a period of 5 days to a hypoxic hypobaric atmosphere (0.5 atm). Exposure to hypoxia produced a significant increase in lung tissue XO activity and an increase in the ratio of XO to XD. L-Arginine supplementation in the drinking water prevented the increase in lung XO and the XO-to-XD ratio in hypoxic rats and caused a significant decrease in XO and XD in rats exposed to normoxia. In conclusion, this study suggests that endogenous NO has a significant role in the regulation of XD/XO both in vitro and in vivo. By inhibiting XD/XO activity, NO may have a modulating effect in conditions of hypoxia and hypoxia-reoxygenation, where this enzyme is thought to be important.

Authors+Show Affiliations

Department of Medicine, New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8944732

Citation

Cote, C G., et al. "Regulation of Intracellular Xanthine Oxidase By Endothelial-derived Nitric Oxide." The American Journal of Physiology, vol. 271, no. 5 Pt 1, 1996, pp. L869-74.
Cote CG, Yu FS, Zulueta JJ, et al. Regulation of intracellular xanthine oxidase by endothelial-derived nitric oxide. Am J Physiol. 1996;271(5 Pt 1):L869-74.
Cote, C. G., Yu, F. S., Zulueta, J. J., Vosatka, R. J., & Hassoun, P. M. (1996). Regulation of intracellular xanthine oxidase by endothelial-derived nitric oxide. The American Journal of Physiology, 271(5 Pt 1), L869-74.
Cote CG, et al. Regulation of Intracellular Xanthine Oxidase By Endothelial-derived Nitric Oxide. Am J Physiol. 1996;271(5 Pt 1):L869-74. PubMed PMID: 8944732.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of intracellular xanthine oxidase by endothelial-derived nitric oxide. AU - Cote,C G, AU - Yu,F S, AU - Zulueta,J J, AU - Vosatka,R J, AU - Hassoun,P M, PY - 1996/11/1/pubmed PY - 1996/11/1/medline PY - 1996/11/1/entrez SP - L869 EP - 74 JF - The American journal of physiology JO - Am J Physiol VL - 271 IS - 5 Pt 1 N2 - We have previously shown that nitric oxide (NO) donors, such as nitrosoglutathione, inhibit endothelial cell (EC) xanthine dehydrogenase (XD)/xanthine oxidase (XO) activity. The purpose of this study was to assess whether endothelial-derived NO plays any role in the regulation of intracellular XD/XO. We exposed rat pulmonary microvascular EC to L-arginine (precursor of NO) or inhibitors of nitric oxide synthase (NOS), i.e., NG-nitro-L-arginine methyl esther (L-NAME) and NG-nitro-L-arginine, in conditions of normoxia, hypoxia, and hypoxia followed by reoxygenation. Hypoxia alone caused a 1.9- and a 6.6-fold increase in XO and a 5-fold increase in XO + XD activities after 24 and 48 h of exposure, respectively. The combination of hypoxia and L-NAME (300 microM) treatment amounted at 48 h to a 10- and 7.5-fold increase in XO and XO + XD activities, respectively, compared with normoxic untreated cells. L-NAME also prevented the decline in XD/XO activity that occurred in untreated EC after hypoxia-reoxygenation. On the other hand, treatment with L-arginine caused a dose-dependent decrease in XD/XO activity in hypoxic EC compared with cells provided with L-arginine-free medium. In separate experiments, we assessed the role of L-arginine supplementation on the in vivo regulation of lung XD/XO by exposing male adult Sprague-Dawley rats for a period of 5 days to a hypoxic hypobaric atmosphere (0.5 atm). Exposure to hypoxia produced a significant increase in lung tissue XO activity and an increase in the ratio of XO to XD. L-Arginine supplementation in the drinking water prevented the increase in lung XO and the XO-to-XD ratio in hypoxic rats and caused a significant decrease in XO and XD in rats exposed to normoxia. In conclusion, this study suggests that endogenous NO has a significant role in the regulation of XD/XO both in vitro and in vivo. By inhibiting XD/XO activity, NO may have a modulating effect in conditions of hypoxia and hypoxia-reoxygenation, where this enzyme is thought to be important. SN - 0002-9513 UR - https://www.unboundmedicine.com/medline/citation/8944732/Regulation_of_intracellular_xanthine_oxidase_by_endothelial_derived_nitric_oxide_ L2 - https://journals.physiology.org/doi/10.1152/ajplung.1996.271.5.L869?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -