Summary
An endogenous humoral factor which inhibits the sodium- and potassium-activated adenosine triphosphatase (Na-K-ATPase) enzyme in vitro has been incriminated recently of playing a pathogenetic role in experimental and human hypertension. The present study was therefore performed in six healthy volunteers to investigate the hemodynamic consequences of an inhibition of this enzyme by ouabain, a potent and specific inhibitor of Na-K-ATPase. In addition, the role of intracellular calcium as a potential mediator was studied indirectly by the administration of nifedipine, a potent calcium entry blocker with predominant vasodilator properties. Intravenous administration of 8.5 µg ouabain/kg body weight inhibited red blood cell (RBC) — Na-K-ATPase by 49% which was accompanied by a significant increase in RBC — ATP and a decrease in intracellular potassium concentrations. This enzyme inhibition resulted in a 24% increase in peripheral vascular resistance. The parallel decrease in cardiac output and heart rate, however, prevented a rise in arterial pressure. This increase in vascular resistance was completely abolished by pretreatment with nifedipine (10 mg orally). In the absence of an effect of nifedipine on Na-K-ATPase, its attenuation of the vasoconstrictor effect of ouabain suggests that the effects of ouabain on the vascular smooth muscle cell are mediated by intracellular calcium. These results demonstrate that inhibition of the Na-K-ATPase enzyme in vivo causes a marked peripheral vaso-constriction. They are also compatible with the concept that an endogenous inhibitor of Na-K-ATPase — in the presence of decreased baroreceptor reflex sensitivity due to blood volume expansion — may play a role in the pathogenesis of human arterial hypertension.
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Abbreviations
- ATP:
-
Adenosine triphosphate
- BP:
-
Blood pressure
- CI:
-
Cardiac index
- HR:
-
Heart rate
- Na-K-ATPase:
-
Sodium-and potassium-activated adenosine triphosphatase
- RBC:
-
Red blood cell
- SVI:
-
Stroke volume index
- TPRI:
-
Total peripheral resistance index
- SEM:
-
Standard error of meanz
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Kramer, H.J., Glänzer, K., Freitag, T. et al. Studies on the role of sodium- and potassium-activated adenosine triphosphatase inhibition in the pathogenesis of human hypertension. Klin Wochenschr 63, 32–36 (1985). https://doi.org/10.1007/BF01537484
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DOI: https://doi.org/10.1007/BF01537484