Fig. 1

Model for the interaction between sequestration of parasitized red blood cells (pRBC), haemolysis, nitric oxide depletion, and vasospasm. Red blood cells containing schizonts adhere to endothelial cells bound by intercellular adhesion molecule-1 (ICAM-1) symbolized by a vertical rectangle and rupture releasing free haemoglobin (oxyHb), the haem moiety of which binds nitric oxide (NO) generated by endothelial nitrix oxide synthase (eNOS) diverting it from diffusion to vascular smooth muscle cells and converting it to methaemoglobin (MetHb). The vascular smooth muscles depicted, can be distant from the site of sequestration anywhere on the arterial side of the circulation. The depletion of NO causes vasoconstriction and increased expression of ICAM-1. Without oxy haemoglobin nitric oxide activates the vascular smooth muscle guanylate cyclase which generates cGMP which via activation of a protein kinase leads to muscle relaxation. Haemoxygenase (HO-1) metabolizes haem into carbon monoxide (CO), iron and biliverdine. CO binds haemoglobin and prevents binding of nitric oxide and hence nitric oxide metabolism