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PREDOMINANCE OF HIGH-MOLECULAR-WEIGHT PLASMA NA+-K+-ATPASE INHIBITOR IN ESSENTIAL-HYPERTENSION

被引：9
作者：
GONICK, HC
WEILER, EWJ
KHALILMANESH, F
WEBER, MA
机构：
[1] Trace Element Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, 8700 Beverly Boulevard, Halper Building
来源：
AMERICAN JOURNAL OF HYPERTENSION | 1993年 / 6卷 / 08期
关键词：
NA+-K+-ATPASE; HYPERTENSION; LOW MOLECULAR WEIGHT PLASMA PROTEIN;
D O I：
10.1093/ajh/6.8.680
中图分类号：
R6 [外科学];
学科分类号：
1002 ; 100210 ;
摘要：
Circulating inhibitors of the transport enzyme, sodium-potassium-activated adenosine triphosphatase (Na+-K+-ATPase), have been shown to be of possible pathogenetic importance in the mechanism of essential hypertension. Although previous studies have demonstrated the presence of both high molecular weight (HMW) and low molecular weight (LMW) natriuretic plasma Na+-K+-ATPase inhibitors, no previous attempts have been made to ascertain whether HMW or LMW forms predominate in hypertension. In this study, plasma samples obtained from 26 patients with essential hypertension, 12 normotensive controls, and six normotensives with a family history of hypertension, were separated into HMW and LMW moieties by passage through a 1 kDa Amicon membrane. The LMW moiety was separated on C18 Sep-Pak cartridges, applying a 10% step-wise acetonitrile trifluoroacetic acid gradient. The HMW moiety was further separated on Sephadex G-75. Sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed that the fraction with inhibitory activity contained a distinct 12 kDa protein band, with staining intensity depending on the presence or absence of hypertension. Na+-K+-ATPase inhibitory activity was found in several LMW fractions, but differences between hypertensives and normotensives were observed in only one fraction (0.29 +/- 0.12 SD v 0.11 +/- .12 mumol/L ouabain equivalents, P < .01). Na+-K+-ATPase inhibitory activity in the HMW fraction was 38 X the inhibitory activity in the LMW fraction and was significantly increased in hypertensives as compared to normotensive controls (10.9 +/- 8.9 v 1.3 +/- 0.8 mumol/L ouabain equivalents, P <.01). Inhibitory activity in both HMW and LMW fractions correlated positively with mean blood pressure. The inhibitory activity of the HMW fraction, but not the LMW fraction, also correlated positively with diastolic blood pressure and inversely with the natural log of plasma renin activity. These results demonstrate that the HMW moiety is the predominant circulating form of the Na+-K+-ATPase inhibitor in hypertension.
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页码：680 / 687
页数：8
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