Skip to content

Volume 17 Supplement 4

Sepsis 2013

We’re sorry, something doesn't seem to be working properly.

Please try refreshing the page. If that doesn't work, please contact us so we can address the problem.

Arginine vasopressin V1a agonist attenuates methicillin-resistant Staphylococcus aureus-induced vascular leakage by inhibiting bradykinin

  • 1,
  • 1,
  • 1,
  • 1 and
  • 1
Critical Care201317 (Suppl 4) :P98

https://doi.org/10.1186/cc12997

  • Published:

Keywords

  • Nitric Oxide
  • Bradykinin
  • Mean Arterial Blood Pressure
  • Lactate Ringer
  • Arginine Vasopressin

Background

Previously, we have shown that methicillin-resistant Staphylococcus aureus (MRSA) sepsis was associated with more severely pronounced vascular leakage compared with Pseudomonas aeruginosa sepsis. We have also demonstrated that the arginine vasopressin V1a receptor (V1aR) agonist significantly attenuated the severity of MRSA-induced vascular leakage [1]. The goal of the present study was to explore mechanistic aspects of V1aR agonist's action.

Materials and methods

Twelve adult female sheep were operatively prepared for chronic study. After 5 days of recovery, tracheostomy was performed under anesthesia and injury was given. The injury consisted of insufflation of cooled cotton smoke (48 breaths) and instillation of 2.5 × 106 CFU MRSA into the lungs by bronchoscope under maintenance isoflurane anesthesia. Following the injury, sheep were awakened, placed on mechanical ventilation and randomly allocated into two groups: control group, saline treated, n = 6; and POV group, treated with intravenous V1aR agonist, Phe2-Orn8-Vasotocin (POV) (Ferring Research Institute, Inc., San Diego, CA, USA), n = 6. The titration of POV was started when mean arterial blood pressure (MAP) dropped by 10 mmHg from the baseline with the initial dose of 30 pmol/minute, which was further adjusted to maintain MAP close to baseline. All sheep were resuscitated with lactated Ringer's solution with initial rate of 2 ml/kg/hour that was further adjusted according to hematocrit. The experiment lasted 24 hours. Plasma levels of nitric oxide (NO; Grease reaction), asymmetric dymethylarginine (ADMA; mass spectrometry) and bradykinin (mass spectrometry) were determined at 0 hours and every 3 hours after the injury.

Results

MRSA-induced plasma levels of NO (nitrite/nitrate) as well as cumulative body fluid were significantly inhibited by V1aR agonist. The treatment with POV also attenuated the MRSA-induced hypotension. The plasma levels of ADMA were higher in the treated group compared with the control at 24 hours after the injury (0.93 ± 0.14 in control, n = 3 vs. 1.23 ± 0.08 in POV, n = 6). In addition, the treatment with POV significantly inhibited the MRSA-induced bradykinin increases at 3 hours after the injury (1.14 ± 0.4 in control vs. 0.52 ± 0.001 in POV, P < 0.05).

Conclusions

Arginine vasopressin V1aR agonist attenuates the severity of MRSA-induced vascular leakage by inhibiting potent permeability factor bradykinin and excessive NO. The V1aR agonist may modulate NO production by promoting the release of endogenous NO synthase inhibitor ADMA.

Authors’ Affiliations

(1)
Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA

References

  1. Rehberg S, et al.: Selective V(1a) agonism attenuates vascular dysfunction and fluid accumulation in ovine severe sepsis. Am J Physiol Heart Circ Physiol 2012, 303: H1245-H1254. 10.1152/ajpheart.00390.2012PubMed CentralView ArticlePubMedGoogle Scholar

Copyright

© Enkhbaatar et al.; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Advertisement