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KMID : 0811720020060000154
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Korean Journal of Physiology & Pharmacology
2002 Volume.6 No. 0 p.154 ~ p.0
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Effect of Ouabain in Regulation of ANP Release
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Cui Xun
Kim Sung-Zoo
Cho Kyung-Woo
Kim Sun-Hee
Jin Jing-Yu
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Abstract
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Ouabain is now considered as an endogenous Na-K-ATPase inhibitor (Goto et al 1998). Also, it was shown to be an endogenous natriuretic steroid hormone. It has been shown that ouabain increases cardiac natriuretic peptide, atrial natriuretic peptide (ANP) (Bloch et al 1988; Cui et al 2002). However, the mechanism by which ouabain increases ANP remains to be defined. Cardiotonic effect of ouabain is well known to be related to modulation of Na+-Ca2+ exchange resulting in an increase of intracellular Ca2+. The purpose of the present study was to define the mechanism responsible for the long-lasting activation of ANP release by ouabain. Experiments have been done in perfused beating rabbit atria allowing measurements of changes in atrial volume during contraction (atrial stroke volume), pulse pressure, transmural extracellular fluid (ECF) translocation and ANP secretion. Ouabain increased atrial myocytic ANP release concomitantly with an increase in atrial dynamics. In the presence of nifedipine, an inhibitor of L-type Ca2+ channel, ouabain-induced increase in ANP release was not observed. In this occasion, nifedipine failed to modulate ouabain-induced accentuation of atrial dynamics. In the presence of staurosporine, a nonselective protein kinase inhibitor, ouabain-induced increases in ANP release and atrial dynamics were not modified. These data suggest that an increase in Ca2+ influx via L-type Ca2+ channel is indirectly involved in the accentuation of ANP release by ouabain. (Supported by KRF 2000-015-FP0023).
Bloch KD, Zamir N, Lichtstein D, Seidman CE, and Seidman JG. Ouabain induces secretion of proatrial natriuretic factor in rat atrial cardiocytes. Am J Physiol 255: E383-E387, 1988.
Goto A and Yamada K. An approach to the development of novel antihypertensive drugs: potential role of sodium pump inhibitors. Trends Pharmacol Sci 19: 201-204, 1998.
Cui X, Kim SZ, Kim SH, Lee HS, and Cho KW. Long-lasting activation of ANP release by ouabain. The 10th Federation meeting of Korean Basic Medical Scientists. Seoul, Korea, May 3-4, 2002.
Source: Korean Journal of Physiology & Pharmacology.2002 Oct;6(Suppl II):S106-S106
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KEYWORD
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atrial natriuretic peptide, L-type Ca2+ channels, ouabain, protein kinase
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