Metabolism of tritiated angiotensin II in anaesthetized rats

Summary The metabolic fate of small doses of a newly prepared, highly radioactive angiotensin II has been studied in anaesthetized rats. Doses of 25 or 100 ng were administered in a single injection and the following parameters were studied: 1. The variation with time of the concentration of total radioactivity in plasma and urine. 2. The nature of this radioactivity, classifying it as protein-bound, free immunoreactive (angiotensin, 2–8 heptapeptide or 3–8 hexapeptide) or free nonimmunoreactive (smaller tyrosine-containing fragments). 3. The distribution of radioactivity in various tissues, including a detailed study of different regions of the brain.The main results are that: 1. angiotensin II and/or metabolites are rapidly removed from the circulation, mainly by tissue uptake and to a lesser extent by urinary excretion (which reached 12% of the dose injected after 1 hour); 2. remaining angiotensin II circulating in the blood is rapidly degraded, presumably by tissue peptidases; 3. radioactivity concentrates in the adrenal glands, kidney, liver and pituitary and does not readily pass the blood-brain barrier; 4. there is a possible binding of angiotensin and metabolites on to plasma proteins.