title: Angiotensin II Moderately Decreases Plasmodium Infection and Experimental Cerebral Malaria in Mice.
abstract: Angiotensin II, a peptide hormone that regulates blood pressure, has been proposed as a protective factor against cerebral malaria based on a genetic analysis. In vitro studies have documented an inhibitory effect of angiotensin II on Plasmodium growth, while studies using chemical inhibitors of angiotensin II in mice showed protection against experimental cerebral malaria but not major effects on parasite growth. To determine whether the level of angiotensin II affects Plasmodium growth and/or disease outcome in malaria, elevated levels of angiotensin II were induced in mice by intradermal implantation of osmotic mini-pumps providing constant release of this hormone. Mice were then infected with P. berghei and monitored for parasitemia and incidence of cerebral malaria. Mice infused with angiotensin II showed decreased parasitemia seven days after infection. The development of experimental cerebral malaria was delayed and a moderate increase in survival was observed in mice with elevated angiotensin II, as confirmed by decreased number of cerebral hemorrhages compared to controls. The results presented here show for the first time the effect of elevated levels of angiotensin II in an in vivo model of malaria. The decreased pathogenesis observed in mice complements a previous human genetic study, reinforcing the hypothesis of a beneficial effect of angiotensin II in malaria.
authors.affiliation: New York University School of Medicine, Dept. of Microbiology, Division of Parasitology, New York, New York, United States of America.
authors.forename: Julio
authors.initials: J
authors.lastname: Gallego-Delgado
authors.affiliation: New York University School of Medicine, Dept. of Microbiology, Division of Parasitology, New York, New York, United States of America.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Baravian
authors.affiliation: New York University School of Medicine, Dept. of Microbiology, Division of Parasitology, New York, New York, United States of America.
authors.forename: Innocent
authors.initials: I
authors.lastname: Edagha
authors.affiliation: New York University School of Medicine, Dept. of Microbiology, Division of Parasitology, New York, New York, United States of America.
authors.forename: Maureen C
authors.initials: MC
authors.lastname: Ty
authors.affiliation: Cellular Biology in Renal Diseases Laboratory, IIS-Fundación Jiménez Díaz/Universidad Autónoma Madrid, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Ruiz-Ortega
authors.affiliation: New York University School of Medicine, Dept. of Microbiology, Division of Parasitology, New York, New York, United States of America; Department of Pathogenic Biology, Third Military Medical University, Chongqing, China.
authors.forename: Wenyue
authors.initials: W
authors.lastname: Xu
authors.affiliation: New York University School of Medicine, Dept. of Microbiology, Division of Parasitology, New York, New York, United States of America.
authors.forename: Ana
authors.initials: A
authors.lastname: Rodriguez
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D008288:Malaria / Q000097:blood / Q000469:parasitology / Q000517:prevention & control*; D016779:Malaria, Cerebral / Q000097:blood / Q000469:parasitology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D018512:Parasitemia / Q000097:blood / Q000469:parasitology / Q000517:prevention & control*; D010962:Plasmodium berghei / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D014662:Vasoconstrictor Agents; D000804:Angiotensin II