Article

The Hormone Angiotensin: A Chemical and Pharmacologic Survey

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Abstract

WITH diseases of multiple origin, such as hypertension, much time is often required for a detailed study of only one facet of the entire problem. Our interests have been broadly directed toward hypertensive disease originating with the kidney, more specifically toward the study of the renin-angiotensin pressor system, and its relationship to normal and abnormal blood pressure.

Reduction of blood flow through the kidney, as illustrated by a Goldblatt clamp on the renal artery,1 can lead to the release of the enzyme renin by the kidney. In the blood, renin reacts with an α-2 globulin, called renin-substrate, to liberate a decapeptide angiotensin I. Neither renin nor angiotensin I is a pressor agent. However, an enzyme present in blood rapidly converts angiotensin I to an octapeptide, angiotensin II, which is the most potent pressor substance known. This process is summarized by the chemical reactions indicated in Figure 1.

The sequence of the first 14 amino acids in renin-substrate protein was determined by Skeggs and his group2 in 1957. Angiotensins I and II from horse blood were shown by Skeggs, Lentz, Kahn, Shumway, and Woods3 to have the sequence shown in Figure 1. Angiotensin I from beef blood has the same sequence of amino acids except that valine is substituted for isoleucine in position 5,4 while angiotensin from hog blood is identical with that from horse blood.5 The final proof for the sequence of amino acids in angiotensin II came with its synthesis by Bumpus and the group at the Cleveland Clinic6 . . .


 

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