Although it was tempting to speculate that cell-surface-localized ACE could serve as a receptor for L. interrogans, as the enzyme is expressed by endothelial cells and proximal tubule epithelial cells [36] , and is therefore open to possible competition by the lisinopril, this is not consistent with our results to date. However, ACE2 is not inhibitable by lisinopril, but is a receptor for the SARS virus [37] , so there is precedent for ACE proteins serving as receptors for pathogens. It is also possible that the effect of lisinopril in our system is not related to ACE inhibition, but is instead due to additional effects of lisinopril, such as inhibition of isoprenoid synthesis, which is required for the post-translational modification of Rho GTPases, which in turn regulate the actin cytoskeleton [38] . In turn, this may lead to increased NO synthesis, which is protective of endothelial function in the face of a variety of insults. Given that doxycycline also has endothelial protective effects [39] , and that doxycycline is effective in treating leptospirosis [40] , our results may also provide a starting point for investigation into possible combinatorial therapeutic approaches to reduction of endothelial damage and consequent organ damage in human populations during leptospirosis outbreaks. Should this combinatorial approach prove useful in animal models, consideration as a focused approach to the treatment of human leptospirosis is warranted. The 1 mM dose shown in Figure 5 is at the high end of the physiologically relevant dosing range for humans, but administration of an antihypertensive to a patient with clinical manifestations of leptospirosis would be contraindicated, as further depression of blood pressure levels would be potentially lethal. However, in outbreak situations, this agent could potentially help to reduce endothelial damage if administered to affected populations as soon as an outbreak situation is recognized, prior to exposure of the majority of the population to pathogenic Leptospira species. In addition, protective effects of lisinopril were maintained even at a dose of 100 nM, which is well within the range routinely used in humans ( Figure 6 ). It will also be interesting to investigate the possibility that, on a population basis, patients on lisinopril fare better than patients not on this therapy during leptospirosis outbreaks.