Opposed circulating plasma levels of endothelin-1 and C-type natriuretic peptide in children with Plasmodium falciparum malaria

Background: Molecular mechanisms involved in the pathogenesis of severe Plasmodium falciparum malaria (SM), are not yet fully understood. Both endothelin-1 (ET-1) and C-type natriuretic peptide (CNP) are produced by vascular endothelium and act locally as paracrine regulators of vascular tone, ET-1 being a potent vasoconstrictor and CNP having strong vasorelaxant properties. Methods: Plasma levels of ET-1 and N-terminal fragments of CNP (NT-proCNP) were studied on admission and after 24 hours of treatment, using enzyme-linked-immunosorbent-assay (ELISA) technique, in Gabonese children with severe falciparum malaria (SM, n = 50), with uncomplicated malaria (UM, n = 39) and healthy controls (HC, n = 25). Results: Compared to HC, malaria patients had significantly higher plasma levels of ET-1 and significantly lower levels of NT-proCNP (p < 0.001 and p < 0.024 respectively). Plasma levels of NT-proCNP were additionally decreased in SM patients compared to HC (p = 0.034), whereas UM was not significantly different to HC. In the SM group we found a trend towards lower ET-1 levels compared to UM (p = 0.085). Conclusion: In the present study, an imbalance between the vasoconstricitve and vasorelaxant endothelium-derived substances ET-1 and CNP in the plasma of children with falciparum malaria is demonstrated, presumably in favor of vasoconstrictive and pro-inflammatory effects. These results may indicate involvement of ET-1 and CNP in malaria pathogenesis. Furthermore, results of lower ET-1 and CNP levels in SM may reflect endothelial cell damage.