Although leucocytes are targets of renin-angiotensin system (RAS) effector molecules and RAS-modulating drugs exert immunomodulatory effects, their impact on Trypanosoma cruzi infection remains poorly understood. By using the framework of a systematic review, we integrated the preclinical and clinical evidence to investigate the relevance of angiotensin-inhibiting drugs on T. cruzi infections. From a comprehensive and structured search in biomedical databases, only original studies were analysed. In preclinical and clinical studies, captopril, enalapril and losartan were RAS-modulating drugs used. The main in vitro findings indicated that these drugs increased parasite uptake per host cells, IL-12 expression by infected dendritic cells and IFN-γ by T lymphocytes, in addition to attenuating IL-10 and IL-17 production by CD8 + T cells. In animal models, reduced parasitaemia, tissue parasitism, leucocytes infiltration and mortality were often observed in T. cruzi-infected animals receiving RAS-modulating drugs. In patients with Chagas’ disease, these drugs exerted a controversial impact on cytokine and hormone levels, and a limited effect on cardiovascular function. Considering a detailed evaluation of reporting and methodological quality, the current preclinical and clinical evidence is at high risk of bias, and we hope that our critical analysis will be useful in mitigating the risk of bias in further studies.

Producers have the possibility to combat human-induced dryland salinity by planting salt-tolerant plants such as saltbush. Saltbush has the potential to be used as a source of food for livestock at a time and place where pasture is not viable. However, saltbush contains high concentrations of sodium chloride salt and some other anti-nutritional factors that have the potential to affect feed and water intake and, directly or indirectly, the reproductive capacity of sheep. High-salt diet during gestation induces a small modification of the activity of the renin-angiotensin system (RAS) that has an important role in the maintenance of the salt-water balance in non-pregnant and pregnant sheep. In contrast, the main effect of salt ingestion during pregnancy is observed on the biology of the offspring, with changes in the response of the RAS to salt ingestion and altered thirst threshold in response to an oral salt ingestion. These changes, observed later in life, are the result of fetal programming following the ingestion of salt by the mother. It seems that the exposure to salt during pregnancy could provide an advantage to the offspring because of this adaptive response. The response may be particularly useful, for example, when grazing herbivores are fed halophytic forages adapted to saline soils.

The short-term effect of intravenous (i.v.) angiotensin converting enzyme (ACE) inhibitor enalaprilat in 10 critically ill patients, being ventilated with positive end-expiratory pressure (PEEP), on sodium and water excretion was investigated. Mean arterial pressure (MAP) decreased. Heart rate and central venous pressure (CVP) did not change. Glomerular filtration rate (GFR), urine volume (V) and sodium excretion (UNaV) decreased in two patients with reduced MAP. GFR, V and UNaV increased in two patients with decreased MAP. No relation between changes in MAP and excretion was observed in six patients. ACE decreased in all patients. Plasma renin activity increased, aldosterone decreased, while atrial natriuretic peptide as well as antidiuretic hormone did not change. Enalaprilat did not facilitate sodium and water excretion during ventilation with PEEP. Decreased MAP indicates that the investigated patients were very dependent on their renin-angiotensin system to maintain systemic perfusion pressure. Base-line MAP and CVP values were no predictors of haemodynamic and excretory changes following acute ACE inhibition.