Experimental malaria: the in vitro and in vivo blood pressure paradox.

OBJECTIVE: Malaria causes more deaths worldwide than any other parasitic disease. Many aspects of the biology that governs the pathogenesis of this parasite are still unclear. Therefore insight into the complexity of the pathogenesis of malaria is vital to understand the disease, particularly as it relates to blood pressure. METHODS: In vivo and in vitro experimental models were used for this study. In the in vivo study, mean arterial pressure, pulse rates and heart rates were recorded by cannulation of the carotid artery of rats. In the in vitro study, ring preparations of blood vessels from the rat aorta were studied using standard organ bath techniques. Dose-response curves for phenylepherine (PE) - and acetylcholine (Ach) -induced relaxation were constructed for rings pre-contracted with PE. RESULTS: Our results showed a significant (p < 0.05) reduction in the mean arterial pressure and pulse rates, while the heart rates remained unaltered in rats with malaria parasites, compared with the controls. Incubation of rat aortic rings with parasitised blood resulted in a significant (p < 0.05) increase in maximum contractile response to phenylephrine in the rat aortic rings but there was no effect on the baseline. The dose-response curve showed a significant (p < 0.05) leftward shift following the addition of parasitised blood and the EC(70) (M) values increased from 7 × 10(- 7) to 5 × 10(-6) M. Following exposure to parasitised blood, the magnitude of Ach-induced relaxation responses reduced significantly (p < 0.05) from 73 ± 3.6 to 24.75 ± 7.25% in the rat aortic rings. CONCLUSIONS: The results suggest that malaria parasitaemia caused in vivo reduction in blood pressure, and enhanced the responses to contractile agents and reduced relaxation responses to acetylcholine in vitro. This appears to be a paradox but is explainable by the complex cardiovascular control mechanisms in vivo. This may be independent of direct action on vascular smooth muscle.

Altered vascular reactivity induced by malaria parasites.

OBJECTIVE: In this study, we have examined the possibility that there is altered vascular reactivity due to the direct interaction between parasitized erythrocytes and vascular endothelial cells. METHOD: Ring preparations of rat aorta were studied using standard in vitro techniques, the rings were mounted in 20 ml organ baths containing PSS under an initial load of 1 g, maintained at 37 degrees C at pH 7.4 and isometric contractions were recorded electronically. Rings were allowed 90 minutes to equilibrate before the commencement of the various protocols: Dose responses to phenylephrine (PE) and other vasoactive agents (high-K+). Acetylcholine (Ach)--induced relaxation in phenylephrine-contracted rings (pre-contraction was induced by EC70 concentration of phenylephrine). Ach-induced relaxation in PE-precontracted, endothelium-denuded rings. Also, relaxation responses to acetylcholine was investigated through application of a single. (EC70) concentration of acetylcholine in rings exposed to blood with varying concentrations and dilutions of parasitized blood and varying durations of exposure. RESULTS: Incubation with parasitized blood resulted in a significant increase in maximum contractile response to phenylephrine in the rat aortic rings (p < 0.05) but no effect to the base line. Analysis of the whole dose-response curve (using paired t-test) showed a significant left-ward shift following the addition of parasitized blood (p < 0.05), EC70 (M) values increasing from 7 x 10(-7) to 5 x 10(-6)M. Following exposure to parasitized blood, the magnitude of Ach-induced relaxation responses reduced significantly from 73 +/- 3.6 to 24.75 +/- 7.25% in rat aortic rings (p < 0.05). Ach relaxations were significantly enhanced (p < 0.05) at 5-minute exposure; however at longer durations, Ach-relaxations were variable and inconsistent. The lesser the dilution, due to increased volume of parasitized blood, the lesser the relaxation response. Following endothelium removal, there was a marked impairment in endothelium-dependent relaxation responses to ACh in both the control and incubated vessels. Exposure to parasitized blood did not significantly alter contractile responses induced by potassium depolarization. CONCLUSIONS: This gives evidence in support of an endothelium-dependent action of malaria parasites as vascular effects of malaria parasites are mediated, at least in part, via endothelium-dependent mechanism(s).

Specificity of vascular reactivity and altered response in experimental malaria.

OBJECTIVE: Adherence of erythrocytes infected with Plasmodium falciparum (P falciparum) to microvascular endothelial cells (sequestration) is considered to play an important role in parasite virulence and pathogenesis. In this study, we have examined the possibility that there is altered vascular reactivity due to the direct interaction between the parasitized erythrocytes and vascular endothelial cells and that it could be tissue specific. METHOD: Ring preparations of blood vessels from the rabbit carotid and rat aorta were studied using standard organ bath techniques. Dose response curves for phenylephrine (PE) and acetylcholine (Ach)-induced relaxation were constructed in rings pre-contracted with PE. RESULTS: Incubation of rat aortic rings with parasitized blood resulted in a significant (p < 0.05) increase in maximum contractile response to phenylephrine in the rat aortic rings but there was no effect on the rabbit carotid artery. The dose-response curve showed a significant (p < 0.05) left-ward shift following the addition of parasitized blood. Parasitised blood had no effect on baseline in both tissues. Following exposure to parasitized blood, the magnitude of Ach-induced relaxation responses reduced significantly (p < 0.05) in rat aortic rings and (p < 0.05) in rabbit carotid rings; relaxations to acetylcholine was more pronounced in the aortic compared to the carotid rings. CONCLUSIONS: Malaria altered vascular reactivity through an endothelium-dependent mechanism. The regulation of vascular tone by various vasoactive agents following exposure to malaria parasites might be altered in a vessel-specific manner. This may contribute to or exacerbate the abnormal haemodynamics observed in the microcirculation of numerous vascular beds in malaria.