Role of the lung in angiotensin metabolism.

The detection and properties of the enzyme which converts angiotensin I to angiotensin II (converting enzyme) are reviewed. Converting enzyme, which is found principally in the lung, is probably responsible in the intact animal for the conversion of angiotensin I to angiotensin II under physiological conditions, the lung thus being the principle site of conversion. The enzyme is distributed in the endothelial cells of the pulmonary capillaries. Conversion of angiotensin I to angiotensin II depends on the area of the vascular bed and the rate of blood flow through the pulmonary circulation. The lungs, in addition to their central role in respiration, play an important part in the metabolism of some vasoactive sub­ stances. As long ago as 1925, Starling and Vemey58 showed that the isolated kidney could not be perfused using a simple cir­ cuit because of vasoconstriction produced by the defibrinated blood. As the effect could be overcome by perfusing the kidney from a heart-lung preparation, they sug­ gested that blood was “detoxicated” in the lungs. The vasoconstrictor was later identi­ fied as 5-hydroxytryptamine;43 about 98 percent of 5HT infused intravenously dis­ appeared in a single passage through the lungs of the anesthetized dog.80 The protective action of the lungs against the potentially harmful effects on the arterial system of vasoactive chemicals has been demonstrated for other substances. These are destroyed by enzymes or stored in reticuloendothelial cells and later re­ leased in small amounts. Noradrenaline,27 bradykinin,18 and prostaglandins Ei, E 2 and F2«19 are removed to the extent of 30 per­ cent, 80 percent and 95 percent, respec­ tively, in one passage through the pul­ monary circulation. In contrast, the lung has an activating effect on angiotensin, the almost inactive angiotensin I being almost completely con­ verted into the highly potent vasoconstric­ tor angiotenin II in a single lung passage.33 The mechanism of the conversion forms the main theme of this paper. A powerful method of identifying and assaying vasoactive substances is the bloodbathed organ technique,61*83 in which blood is superfused,22 i.e. bathes the out­ side, over a test organ. Blood, suitably anticoagulated, is pumped from an artery of the animal under investigation and al­ lowed to flow over a series of up to three isolated test organs, selected from rat colon, cat jejunum, chick rectum, rabbit rectum and rat stomach. Organs and blood are kept at 37 °C. Contraction or relaxation of the test organs is suitably recorded.