Beneficial effects of statins on the microcirculation during sepsis: the role of nitric oxide

This review describes the laboratory evidence and microvascularmechanisms responsible for the beneficial effects of statinsin sepsis. During sepsis, changes occur within the microcirculationincluding alterations in arteriolar tone influencing blood pressure,adaptations to endothelial cell integrity causing leakage ofproteins and macromolecules, and adhesion and migration of leucocytesthrough the vascular endothelium. Statins are widely used ascholesterol-lowering agents, but appear to have anti-inflammatoryactions during sepsis. We have discussed the effects of statinson specific pathological processed within the microcirculationand focused on the role of nitric oxide (NO). The main mechanism by which statins appear to be an effectivetreatment for sepsis is increased expression of endothelialnitric oxide synthase (eNOS), in conjunction with down-regulationof inducible nitric oxide synthase. Combined, this results inan increase in physiological concentrations of NO, thus restoringendothelial function. Laboratory studies have therefore suggestedthat enhancement of eNOS activity during sepsis may lead torestoration of microvascular tone, maintenance of microvascularintegrity, and inhibition of cell adhesion molecules. However,other mechanisms independent of lipid-lowering effects, includingantioxidant activity and alterations in the development of vascularatherosclerosis, may also contribute to the beneficial effectsof statins. We have also addressed the influence on the effectsof statins of lipid solubility and pre- and pro-phylactic administration.