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Kwon, H. Moo
Inflammation and Kidney Disorder Lab
Research Interests
  • TonEBP, Obesity, Cancer, Chronic inflammatory diseases, Brain disorder, Kidney disorders, Genomic instability

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Chronic ouabain treatment induces vasa recta endothelial dysfunction in the rat

Cited 12 times inthomson ciCited 11 times inthomson ci
Title
Chronic ouabain treatment induces vasa recta endothelial dysfunction in the rat
Author
Cao, ChunhuaPayne, KristieLee-Kwon, WhaseonZhang, ZhongLim, Sun WooHamlyn, JohnBlaustein, Mordecai PKwon, H. MooPallone, Thomas L
Keywords
Blood flow; Kidney; Medulla; Microcirculation; Nitric oxide
Issue Date
200901
Publisher
AMER PHYSIOLOGICAL SOC
Citation
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, v.296, no.1, pp.f98 - f106
Abstract
Cao C, Payne K, Lee-Kwon W, Zhang Z, Lim SW, Hamlyn J, Blaustein MP, Kwon HM, Pallone TL. Chronic ouabain treatment induces vasa recta endothelial dysfunction in the rat. Am J Physiol Renal Physiol 296: F98-F106, 2009. First published October 22, 2008; doi: 10.1152/ajprenal.90429.2008.-Descending vasa recta (DVR) are 15-mu m vessels that perfuse the renal medulla. Ouabain has been shown to augment DVR endothelial cytoplasmic Ca(2+) ([Ca(2+)](CYT)) signaling. In this study, we examined the expression of the ouabain-sensitive Na-K-ATPase alpha 2 subunit in the rat renal vasculature and tested effects of acute ouabain exposure and chronic ouabain treatment on DVR. Immunostaining with antibodies directed against the alpha 2 subunit verified its expression in both DVR pericytes and endothelium. Acute application of ouabain (100 or 500 nM) augmented the DVR nitric oxide generation stimulated by acetylcholine (ACh; 10 mu M). At a concentration of 1 mM, ouabain constricted microperfused DVR, whereas at 100 nM, it was without effect. Acute ouabain (100 nM) did not augment constriction by angiotensin II (0.5 or 10 nM), whereas L-nitroarginine methyl ester-induced contraction of DVR was slightly enhanced. Ouabain-hypertensive (OH) rats were generated by chronic ouabain treatment (30 mu g.kg(-1).day(-1), 5 wk). The acute endothelial [Ca(2+)](CYT) elevation by ouabain (100 nM) was absent in DVR endothelia of OH rats. The [Ca(2+)](CYT) response to 10 nM ACh was also eliminated, whereas the response to 10 mu M ACh was not. The endothelial [Ca(2+)](CYT) response to bradykinin (100 nM) was significantly attenuated. We conclude that endothelial responses may offset the ability of acute ouabain exposure to enhance DVR vasoconstriction. Chronic exposure to ouabain, in vivo, leads to hypertension and DVR endothelial dysfunction, manifested as reduced [Ca(2+)](CYT) responses to both ouabain- and endothelium-dependent vasodilators.
URI
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DOI
http://dx.doi.org/10.1152/ajprenal.90429.2008
ISSN
1931-857X
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