LOW-DOSE PROSTACYCLIN HAS POTENT CAPILLARY PERMEABILITY-REDUCING EFFECT IN CAT SKELETAL-MUSCLE IN-VIVO

The dose-response effects of intravenous infusion of prostacyclin on c apillary permeability (the capillary filtration coefficient technique) , hydrostatic capillary pressure, transcapillary filtration, and vascu lar tone were analyzed in vivo on cat skeletal muscle from a normal an d an increased permeability level. Increased permeability was accompli shed by intra-arterial infusion of tumor necrosis factor-alpha or hist amine. Permeability effects of bradykinin were also analyzed. Prostacy clin decreased capillary permeability by 8% at a dose of 0.1 ng.kg(-1) .min(-1) and at most by 30% below control attained at 2 ng.kg(-1).min( -1), also with no effect on vascular tone and hydrostatic capillary pr essure. The permeability increase by tumor necrosis factor-alpha and h istamine (by 54 and 73%) was more than counteracted by the simultaneou s infusion of prostacyclin at 2 ng.kg(-1).min(-1). The vasodilator eff ect of tumor necrosis factor-alpha was also restituted. Indomethacin ( prostacyclin inhibitor)-induced increase in capillary permeability (25 %) was more than restituted by prostacyclin at 2 ng.kg(-1).min(-1). Su rprisingly, bradykinin decreased capillary permeability. We conclude t hat endogenous prostacyclin may be a physiological regulator of capill ary permeability and that low-dose prostacyclin infusion may have clin ical relevance in states of increased permeability.