Ang II inhibits <i>P</i>. <i>falciparum</i> growth <i>in vitro</i> and <i>P</i>. <i>berghei</i> growth in mice.

<p>A) Parasite levels in cultures of <i>P</i>. <i>falciparum</i> incubated with different concentrations of Ang II <i>in vitro</i>. Ratio of day 0 (initial parasitemia) to day 1 (right axis, circles) and percentage rupture of infected erythrocytes (left axis, squares). B) Parasitemia was determined in groups of mice that were infected with <i>P</i>. <i>berghei</i> (day 0) and had been subjected (n = 8; circles) or not (n = 8; squares) to implantation of subcutaneous mini-pumps releasing saline buffer. C) Parasitemia of groups of mice infected with <i>P</i>. <i>berghei</i>: control (n = 14; circles), implanted with intradermal micro-pumps releasing Ang II at 100 ng/kg/min (n = 15; squares) or 500 ng/kg/min (n = 15; triangles). Number of surviving mice in each group are indicated in the table. Mice numbers decrease due to experimental cerebral malaria induced death (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0138191#pone.0138191.g002" target="_blank">Fig 2B</a>). (B,C) Statistical analysis by t-Student (B) and Kruskal Wallis (C). Average plus standard error is shown. * <i>p</i><0.05; **<i>p</i><0.01; ***<i>p</i><0.001.</p

Ang II decreases brain hemorrhages, delays experimental cerebral malaria and increases survival of mice.

<p>Groups of mice as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0138191#pone.0138191.g001" target="_blank">Fig 1C</a>, control (black circles); Ang II at 100 and 500 ng/kg/min (black squares and triangles, respectively) were observed twice a day for determination of cerebral malaria based on neurological symptoms (as described in methods) (A) and survival (time of euthanasia) (B). Kaplan-Meier analyses were conducted to determine differences among the groups. Cerebral malaria and survival distribution of the groups were significantly different (<i>p</i><0.010 and <i>p</i><0.013, respectively). Pairwise log rank comparison after applying Bonferroni correction (statistical significance accepted at the <i>p</i><0.0167 level) showed that for cerebral malaria there was a statistically significant difference between control <i>vs</i> Ang II (100) (<i>p</i> = 0.0021) but not <i>vs</i> Ang II (500) (<i>p</i> = 0.0258). For survival, both Ang II groups showed significant differences vs control group (<i>p</i> = 0.0087 and <i>p</i> = 0.0100 for Ang II (100) and Ang II (500) <i>vs</i> control, respectively). No significant differences were found between angiotensin groups, Ang II (100) and Ang II (500) (<i>p</i> = 0.511 and <i>p</i> = 0.524 for cerebral malaria and survival respectively). Histological sections of the brains of mice control (C), Ang II at 100 ng/kg/min (D) and Ang II at 500 ng/kg/min (E) were analyzed for the presence and size of hemorrhages. Bar is 50μm. Quantification of the number (F) and size (G) of hemorrhages per mm². Mice that were sacrificed with a cerebral malaria score of 3 (black circles), 4 (blue circles) or 5 (red circles) and mice that did not develop cerebral malaria (gray circles) are indicated. Average values for each mouse are shown. **<i>p</i><0.01 by ANOVA. No significant differences were observed between groups in (G).</p