Angiotensin II-Linked Hypothesis to Understand the Advantage of the Coevolution of Hypertension and Malaria: "Sympathy for the Devil".

Abstract

In the article “The high blood pressure-malaria protection hypothesis” published in this issue, Gallego-Delgado et al1 hypothesize that hypertension confers an evolutionary advantage and protection for populations chronically exposed to Plasmodium falciparum infection.1 The authors suggest that hypertension, which is more frequent in the areas with endemic malaria, may protect affected patients from the development of cerebral malaria, which is the most lethal complication of this disease. According to the authors1 both preclinical and clinical evidence support the possibility that the key factor in the hypertension–malaria relationship is angiotensin II (Ang II), whose levels tend to be higher in populations living in endemic areas. Indeed, Ang II seems to have beneficial effects on the brain–blood barrier integrity (most likely by binding to Ang II type 2 receptors [AT2] on endothelial cells), which might exert, through a variety of mechanisms, a cerebroprotective effect during malaria infection.1 Article, see p 1071 The evolutionary role of the renin–angiotensin system in the development of species is indeed suggested by several considerations. The renin–angiotensin system is a biological system almost ubiquitary in humans body, and it is present in the whole phylogenetic scale of animals from simple organisms to humans.2,3 Its major biological effector in mammals is Ang II. In the evolution of the human species, renin–angiotensin system may have favored the upright …