Effect of plasma from murine experimental cerebral malaria infection on constriction of aortic rings

Authors

  • GS Sanches
  • TSB Marins
  • CG Pontes
  • F Gomes
  • H Ackerman
  • LJM Carvalho

Abstract

Introduction. Endothelial dysfunction associated with low nitric oxide (NO) bioavailability is thought to be involved in the pathogenesis of cerebral malaria (CM), yet the mechanisms of vascular dysfunction remain elusive. Herein, we tested whether plasma changes vascular tension of aortic rings and whether this effect differs in plasma from mice with experimental CM (ECM). Methods. Thoracic aortas from 8-12 weeks C57BL/6 mice were dissected in ice-cold Krebs-HEPES (KH) buffer. Aorta segments were divided into 2mm rings. Isometric tension was recorded via wire myography. To assess endothelial function, 10μM phenylephrine was added, followed by 10μM acetylcholine. Rings exhibiting ≥70% relaxation was selected and stimulated with increasing concentrations of plasma Control or ECM (0.1%, 0.3%, 1.0% and 3.0%). Next, 10μM L-NAME, 10μM nifedipine and 10mM EGTA were sequentially added. Results were expressed in grams force (g) difference from the baseline and presented as mean±SD (n=5). Results. Regression analysis showed control plasma induced an increased tension on 0.1% (-0.003g±0.01), 0.3% (-0.0013g±0.02), 1.0% (0.031g±0.04) and 3.0% (0.12g±0.07, r2 = 0.62, p<0.0001) stimulation. L-NAME increased the tension to 3.0% plasma to 0.59g±0.21 (p=0.003). Nifedipine decreased the tension to 0.08g±0.07 (p=0.009), and calcium chelation with EGTA further decreased the tension to -0.003g±0.05 (p=0.005). ECM plasma displayed a similar dynamic, inducing constriction at 3.0% (0.08g±0.06, p=0.007) that was greater after L-NAME inhibition (0.58g±0.3, p=0.008). Linear regression showed no difference in functional response between control and ECM plasma (p=0.2). Conclusion. Control and ECM plasma induces constriction of aortic rings and simultaneously elicits a NO synthase-dependent counterbalancing vasodilatory signal.

Scientific Focus Area: Microbiology and Infectious Diseases

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