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Effects of homocysteine on intracellular nitric oxide and superoxide levels in the renal arterial endothelium. Am J Physiol Heart Circ Physiol 2002 Sep;283(3):H1237-43

Date

08/16/2002

Pubmed ID

12181155

DOI

10.1152/ajpheart.00680.2001

Scopus ID

2-s2.0-0036351855   25 Citations

Abstract

The present study was designed to test the hypothesis that homocysteine (Hcys) reduces intracellular nitric oxide (NO) concentrations ([NO](i)) and stimulates superoxide (O.) production in the renal arterial endothelium, thereby resulting in endothelial dysfunction. With the use of fluorescence microscopic imaging analysis, a calcium ionophore, A-23187 (2 microM), and bradykinin (2 microM) were found to increase endothelial [NO](i) in freshly dissected lumen-opened small renal arteries loaded with 4,5-diaminofluorescein diacetate (DAF-2DA; 10 microM). Preincubation of the arteries with L-Hcys (20-40 microM) significantly attenuated the increase in endothelial [NO](i). However, L-Hcys had no effect on NO synthase activity in the renal arteries, as measured by the conversion rate of [(3)H]arginine to [(3)H]citrulline, but it concentration dependently decreased DAF-2DA-sensitive fluorescence induced by PAPA-NONOate in the solution, suggesting that L-Hcys reduces endothelial [NO](i) by its scavenging action. Because other thiol compounds such as L-cysteine and glutathione were also found to reduce [NO](i), it seems that decreased NO is not the only mechanism resulting in endothelial dysfunction or arteriosclerosis in hyperhomocysteinemia (hHcys). By analysis of intracellular O. levels using dihydroethidium trapping, we found that only L-Hcys among the thiol compounds studied markedly increased O. levels in the renal endothelium. These results indicate that L-Hcys inhibits the agonist-induced NO increase but stimulates O. production within endothelial cells. These effects of L-Hcys on [NO](i) and [O.] may contribute to endothelial injury associated with hHcys.

Author List

Li N, Yi FX, Rute E, Zhang DX, Slocum GR, Zou AP

Author

David X. Zhang MD, PhD Associate Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Bradykinin
Calcimycin
Endothelium, Vascular
Enzyme Inhibitors
Homocysteine
Ionophores
Male
Microscopy, Fluorescence
NG-Nitroarginine Methyl Ester
Nitric Oxide
Nitric Oxide Synthase
Rats
Rats, Sprague-Dawley
Renal Artery
Renal Circulation
Superoxides
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a