ABSTRACT
(8-L-[(14)C] phenylalanine) angiotensin I is metabolized in one passage through blood-free lungs. Approximately 20 percent of the radioactivity emerges as angiotensin 11, the remainder as lower homologs. Radioactivity is not retained by the lungs but has the same volume of distribution and mean transit time as blue dextran, a compound unlikely to leave the intravascular space. Plasma membrane fractions of lung are capable of converting angiotensin I to angiotensin II. These data, taken together, indicate the circulating angiotensin I is metabolized by enzymes of the luminal surface of pulmonary endothelial cells.
Subject(s)
Angiotensin II/metabolism , Lung/metabolism , Angiotensin II/analysis , Animals , Carbon Isotopes , Cell Membrane/analysis , Cell Membrane/enzymology , Cell Membrane/metabolism , Chromatography , Coloring Agents , Dextrans/metabolism , Electrophoresis , In Vitro Techniques , Lung/analysis , Lung/cytology , Lung/enzymology , Microscopy, Electron , Nucleotidases/analysis , Perfusion , Phenylalanine/metabolism , RatsABSTRACT
3-H5,6-Prostaglandin F1alpha is largely eliminated from the circulation during a single passage through the pulmonary vascular bed. Its elimination requires cellular uptake. The volume of distribution and the mean transit time of the radioactivity are greater than those of an intravascular marker, blue dextran. The lungs retain 25-30% of the radioactivity, most in the form of a metabolite less polar that PGF1alpha itself. The pulmonary venous effluent contains the same metabolite along with some unmetabolized PGF1alpha. The metabolite can be distinguished from prostaglandins of the A, B, D, E and F series. It is reduced on reaction with borohydride, but reduction does not yield PGF1alpha. NaOH has no effect on the metabolite, a finding that rules out the presence of a beta-hydroxy-ketone configuration of the ring structure. The chromatographic behavior of the metabolite and its reaction with borohydride are those expected of 9,11-hydroxy-15-ketoprostanoic acid.