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Abnormal activation of Na+-K+ pump in aortas from rats with endotoxaemia

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Abstract

A diminished reactivity to several vasoconstrictor agents is usually observed in blood vessels obtained from animals with endotoxic shock. The contractile state of vascular smooth muscle is influenced by the activity of the electrogenical sodium (Na+-K+) pump. Thus, we examined inhibitors and agonists of nitric oxide (NO)-guanosine 3':5'-cyclic monophosphate (cGMP) on contractions to phenylephrine (PE) and relaxations to potassium in isolated aortic segments from rats treated with bacterial endotoxin (lipopolysaccharide, LPS) for 6 h (i.e. to mimic a shock syndrome). Endotoxaemia for 6 h was associated with a severe hypotension and vascular hyporeactivity to noradrenaline and an increased plasma nitrate level in vivo. The PE-induced contraction was attenuated in aortic smooth muscle obtained from rats with endotoxic shock while the potassium-induced relaxation was greater in these preparations. Ouabain dose-dependently inhibited the potassium-induced relaxation in aortas from normal and endotoxaemic rats. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one enhanced the PE-induced contraction in endotoxaemic rats only, whereas it attenuated the difference of potassium-induced relaxation between normal and endotoxaemic rats. In contrast, in aortas obtained from normal rats, 8-bromo-cGMP reduced the PE-induced contraction and enhanced the potassium-induced relaxation to the level as seen in endotoxaemic animals. In aortas obtained from endotoxaemic rats, methylene blue further restored the PE-induced contraction to the normal and abolished the difference of potassium-induced relaxation between normal and endotoxaemic rats. These results suggest that the Na+-K+ pump in the vascular bed of animals with endotoxic shock is abnormally activated and this augmented activation is modulated by cGMP.

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Acknowledgements

This work was supported by grants NSC 89–2320-B-016–019 and NSC 90–2315-B-016–008 from the National Science Council, R.O.C., Taiwan.

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Authors and Affiliations

  1. Department of Physiology, National Defence Medical Centre, Taipei, Taiwan, R.O.C.

    Shiu-Jen Chen

  2. Department of Pharmacology, National Defence Medical Centre, Taipei, Taiwan, R.O.C.

    Kao-Hsiang Chen, Mao-Hsiung Yen & Chin-Chen Wu

  3. Department of Physiology, Medical College of Georgia, Augusta, Georgia, USA

    R. Clinton Webb

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  1. Shiu-Jen Chen
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  2. Kao-Hsiang Chen
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  3. R. Clinton Webb
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  4. Mao-Hsiung Yen
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Correspondence to Chin-Chen Wu.

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Chen, SJ., Chen, KH., Webb, R.C. et al. Abnormal activation of Na+-K+ pump in aortas from rats with endotoxaemia. Naunyn-Schmiedeberg's Arch Pharmacol 368, 57–62 (2003). https://doi.org/10.1007/s00210-003-0762-z

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  • DOI: https://doi.org/10.1007/s00210-003-0762-z

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