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

Background: The changes in microvascular permeability characteristic of pos tinjury inflammation and sepsis may involve dysfunctional regulatory mechan isms at the capillary level. Pericytes, positioned abluminal to microvascul ar endothelium may, by their contractility, contribute to this regulation. Reactive oxygen metabolites (ROMs), well-known participants in lung inflamm ation, may exert an effect on pericytes, leading to changes in permeability and adult respiratory distress syndrome. This study investigates the effec t of ROMs and antioxidants in an established in vitro assay of pericyte con tractility. Methods. Rat lung pericytes were cultured on collagen gel matrices. After e xposure to the ROMs, the surface area of the collagen disks was digitally q uantified (an integrated measure of cellular contraction) at 10 and 30 minu tes. The cells were exposed to hydrogen peroxide and pyrogallol at 10, 100, and 1,000 mu mol/L. Antioxidant effects of catalase (100 mu mol/ L), super oxide dismutase (100 mu mol/L), and pretreatment with vitamin E (1 mmol/L) were quantified. Results: Hydrogen peroxide and pyrogallol induced concentration-dependent r elaxation at 10 minutes. Conversely, concentration-dependent contraction wa s seen at 30 minutes. Catalase completely attenuated both responses, wherea s 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 contrac tion 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 sig naling pathways affecting actin/myosin tone, and late membrane damage causi ng contraction. Either pathway may cause dysfunction in pulmonary capillary fluid regulation.