Fibronectin decreases pulmonary vascular permeability under baseline conditions and after administration of arachidonic acid in rabbit lungs.
In blood- and plasma-free perfused isolated rabbit lungs, the influence of albumin and soluble fibronectin on vascular permeability was investigated. The lungs were perfused with Krebs Henseleit buffer containing no protein (KHB), containing 1 g/100 ml bovine albumin (KHAB) or containing albumin together with 100 micrograms/ml soluble fibronectin. The absence or presence of albumin had no influence on the perfusion pressure, the vascular compliance and the capillary filtration coefficient (CFC), determined by zero time extrapolation of the slope of weight gain which was induced by a sudden venous pressure elevation. Fibronectin caused a slight increase in pulmonary artery pressure, a slight decrease in vascular compliance and an approximately 50% reduction of CFC. In a second set of experiments, KHAB-perfused lungs were stimulated by the administration of 100 microM arachidonic acid (AA) during the second hydrostatic challenge within a sequence of three venous pressure elevations. In the presence of indomethacin, which blocks any significant increase in pulmonary vascular pressure after AA application, this procedure caused an immediate gain in lung weight due to increased pulmonary vascular permeability, with greater than 10-fold increased CFC values subsequent to the AA application. In the presence of 100 micrograms/ml fibronectin, this AA-induced increase in CFC was mitigated to less than 20% of the controls without the glycoprotein, with correspondingly severalfold reduced lung weight gain. In conclusion, the present study provides evidence for a direct influence of circulating soluble fibronectin on lung microvascular integrity and fluid balance under baseline conditions and after stimulation of the pulmonary AA cascade.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D001808:Blood Vessels / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects*; D005353:Fibronectins / Q000494:pharmacology*; D006874:Hydrostatic Pressure; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000098:blood supply*; D010477:Perfusion; D011817:Rabbits; D012709:Serum Albumin / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects
D001095:Arachidonic Acids; D005353:Fibronectins; D012709:Serum Albumin; D016718:Arachidonic Acid; D007213:Indomethacin