Reactive oxygen metabolites induce a biphasic contractile response in microvascular lung pericytes

BACKGROUND: The changes in microvascular permeability characteristic of postinjury inflammation and sepsis may involve dysfunctional regulatory mechanisms at the capillary level. Pericytes, positioned abluminal to microvascular endothelium may, by their contractility, contribute to this regulation. Reactive oxygen metabolites (ROMs), well-known participants in lung inflammation, may exert an effect on pericytes, leading to changes in permeability and adult respiratory distress syndrome. This study investigates the effect of ROMs and antioxidants in an established in vitro assay of pericyte contractility. METHODS: Rat lung pericytes were cultured on collagen gel matrices. After exposure to the ROMs, the surface area of the collagen disks was digitally quantified (an integrated measure of cellular contraction) at 10 and 30 minutes. The cells were exposed to hydrogen peroxide and pyrogallol at 10, 100, and 1,000 micromol/L. Antioxidant effects of catalase (100 micromol/L), superoxide dismutase (100 micromol/L), and pretreatment with vitamin E (1 mmol/L) were quantified. RESULTS: Hydrogen peroxide and pyrogallol induced concentration-dependent relaxation at 10 minutes. Conversely, concentration-dependent contraction was seen at 30 minutes. Catalase completely attenuated both responses, whereas superoxide dismutase had no effect. Vitamin E had no effect at 10 minutes but partially attenuated the contraction seen at 30 minutes. CONCLUSION: ROMs are capable of producing early relaxation and late contraction in cultured lung pericytes. Whereas catalase attenuates both responses, membrane-bound vitamin E only partially attenuates late contraction. This suggests two separate mechanisms: early physiologic relaxation through signaling pathways affecting actin/myosin tone, and late membrane damage causing contraction. Either pathway may cause dysfunction in pulmonary capillary fluid regulation.