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Reversal of lipopolysaccharide-induced hyporeactivity in rat aorta and human mesenteric artery in vitro by orthovanadate
Critical Care volume 9, Article number: P78 (2005)
Endotoxemia is characterised by vascular hyporeactivity (VHR) that is partially caused by the excess of nitric oxide (NO) production. The agent that affects Ca2+ transport or the Ca2+ sensitivity of contraction may theoretically reverse VHR.
The VHR was induced in vitro by incubating (for 6 hours) rat aortal rings, with or without endothelium (± ENDO), or human mesenteric arterial rings (HMA) endothelium intact (+ENDO), with lipopolysaccharide Escherichia coli (LPS) (10-3 g/l). In addition, the preparations (12 groups, n = 7 each) were preincubation (10 min) with various concentrations of sodium-orthovanadate (OV) (10-7, 10-6, or 10-5 M) and then the contractile response to phenylephrine (PE) was examined in vitro.
We found that the presence of endothelium diminished sensitivity to PE in rat aorta (+ENDO, EC50: 5.88 ± 0.11 vs -ENDO, EC50: 6.84 ± 0.15, respectively), a result probably of an overproduction of nitric oxide and potassium channel activation. The preincubation with OV had no effect on sensitivity to PE in rat aorta (± ENDO) and HMA (+ENDO) as compared with corresponding controls (without OV [-OV]). However, preincubation with OV increased maximal tension (Tmax) to PE, as compared with the control (-OV). Tmax (kg/g, dry muscle), control versus OV (concentration): rat aorta (-ENDO): 0.87 ± 0.19 vs 1.42 ± 0.23 (10-7 M), 1.56 ± 0.28 (10-6 M) and 2.33 ± 0.69 (10-5 M); rat aorta (+ENDO): 0.88 ± 0.21 vs 1.53 ± 0.35 (10-7 M), 1.35 ± 0.30 (10-6 M) and 2.55 ± 0.68 (10-5 M); and human mesenteric artery (+ENDO): 1.12 ± 0.23 vs 0.37 ± 0.14 (10-7 M), 2.06 ± 0.21 (10-6 M) and 3.00 ± 0.07 (10-5 M), respectively.
These findings demonstrated that the VHR in rat aorta and human mesenteric artery could be reversed by an inhibition of calcium removal and/or inhibition of tyrosine phosphatase activity. It should be verified whether in human preparations taken from septic patients orthovanadate could have some beneficial effects on vascular hyporeactivity.
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Erber, H., Lehmann, C., Gruendling, M. et al. Reversal of lipopolysaccharide-induced hyporeactivity in rat aorta and human mesenteric artery in vitro by orthovanadate. Crit Care 9, P78 (2005). https://doi.org/10.1186/cc3141
- Nitric Oxide
- Septic Patient
- Tyrosine Phosphatase
- Contractile Response