The Change and Significance of the Na⁺-K⁺-ATPase α-Subunit in Ouabain-Hypertensive Rats

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Ouabain has recently been identified as an endogenous Na⁺-K⁺ pump inhibitor having a close association with hypertension. However, some patients with hypertention do not show high levels of endogenous ouabain (EO), and patients with high EO levels do not necessarily suffer from hypertention. It is believed that the Na⁺-K⁺-ATPase activity in essential hypertension does not undergo homogenous change. The present study was designed, therefore, to investigate the expression and the significance of the Na⁺-K⁺-ATPase α-subunit isoforms in kidney tissue in ouabain-hypertensive rats. Ouabain was administered chronically to establish a model of ouabain-hypertensive rats. Biochemical analysis, cytobiology and sABC immunohistochemistry were they used to assay for expression of Na⁺-K⁺-ATPase α-subunit isoforms in kidney tissue. After the first week of receiving ouabain, 65% (n=13) of rats had hypertension. After the second week, the blood pressure of these 13 hypertensive rats was increased significantly compared to the baseline and control levels (p<0.05). The plasma renin activity was normal, and angiotensin II and aldosterone levels were increased significantly in these rats (p<0.05). But in the other 35% (n=7) of rats of the experimental group, there was no apparent increase in blood pressure after receiving ouabain. The plasma ouabain level in the non-hypertensive subgroup was significantly higher than that in the hypertensive subgroup, but the ⁸⁶Rb intake and the number of ³H-ouabain binding sites did not decrease. The Na⁺-K⁺-ATPase activity showed non-homogeneous changes. In hypertensive rats, the expression levels of ouabain paralleled the degree of hypertension (r=0.88, p<0.05). The positive granules were mainly scattered in the cytoblastoma of the reticular zone of adrenal cortex. There were thus different levels of expression of Na⁺-K⁺-ATPase α-subunit isoforms in this model. In the hypertension subgroup the α₁ was most strongly expressed, followed by the α₂ and α₃ isoforms. But in the non-hypertensive subgroup the order was α₃>α₂>α₁. The positive granular was mainly scattered in the convoluted tubules of the kidney. These results suggest that the high level of ouabain and the change of the Na⁺-K⁺-ATPase α-subunit isoforms may play a critical role in hypertension. (Hypertens Res 2001; 24: 729-734)