Vrbjar N, Javorková V, Pechánová O
Department of Biochemistry, Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Physiol Res. 2002;51(5):475-81.
The aim of this study was to assess the molecular basis of renal Na,K-ATPase disturbances in response to NO-deficient hypertension induced in rats by NO-synthase inhibition with 40 mg/kg/day N(G)-nitro-L-arginine methyl ester (L-NAME) for four weeks. After 4-week administration of L-NAME, the systolic blood pressure (SBP) increased by 30 %. Three weeks after terminating the treatment, SBP recovered to control value. When activating the Na,K-ATPase with its substrate ATP, a 36 % increase in K(m) and 29 % decrease in V(max) values were observed in NO-deficient rats. During activation with Na+, the V(max) was decreased by 20 % and the K(Na) was increased by 111 %, indicating a profound decrease in the affinity of the Na+-binding site in NO-deficient rats. After spontaneous recovery from hypertension, the V(max) remained at the level as in hypertension for both types of enzyme activation. However, in the presence of lower concentrations of substrate which are of physiological relevance an improvement of the enzyme activity was observed as documented by return of K(m) for ATP to control value. The K(Na) value for Na+ was decreased by 27 % as compared to hypertension, but still exceeded the corresponding value in the control group by 55 % thus resulting in a partial restoration of Na+ affinity of Na,K-ATPase which was depressed as a consequence of NO-dependent hypertension.
本研究的目的是评估大鼠因用40mg/kg/天的N(G)-硝基-L-精氨酸甲酯（L-NAME）抑制一氧化氮合酶四周而诱发的一氧化氮缺乏型高血压所导致的肾钠钾ATP酶紊乱的分子基础。给予L-NAME 4周后，收缩压（SBP）升高了30%。在终止治疗三周后，SBP恢复到对照值。在用其底物ATP激活钠钾ATP酶时，在一氧化氮缺乏的大鼠中观察到米氏常数（K(m)）增加36%，最大反应速度（V(max)）值降低29%。在用Na+激活过程中，V(max)降低20%，钠亲和常数（K(Na)）增加111%，表明一氧化氮缺乏的大鼠中Na+结合位点的亲和力显著降低。从高血压自发恢复后，对于两种类型的酶激活，V(max)都保持在高血压时的水平。然而，在存在生理相关的较低底物浓度时，观察到酶活性有所改善，表现为ATP的K(m)恢复到对照值。与高血压时相比，Na+的K(Na)值降低了27%，但仍比对照组的相应值高出55%，从而导致钠钾ATP酶的Na+亲和力部分恢复，该亲和力因一氧化氮依赖性高血压而降低。
