Angiotensinogen angiotensin metabolic pathway

(Last Updated On: October 14, 2022)
Step wise illustration of formation of different types of angiotensin from precursor protein angiotensinogen
A stepwise illustration of the formation of different types of angiotensin from precursor protein angiotensinogen

Angiotensin II from Angiotensinogen

Angiotensin is a group of peptide hormones that contains mainly four types; I, II, III, and IV. However, the biologically active form is angiotensin II. All of these are produced from the single precursor protein angiotensinogen in different steps.

Angiotensinogen is a 453 amino acid long protein that is produced in the liver in response to hormones such as corticosteroids, thyroid hormones, and estrogen. Angiotensinogen is released from the liver into the bloodstream where it is converted into angiotensin I which is an oligopeptide containing 10 amino acid residues (decapeptide). The cleavage of angiotensinogen in the blood circulation is catalyzed by the enzyme renin that is released from the kidney which cleavages of the peptide bond between the Leu and Val of the angiotensinogen.

Angiotensin I has no biological activity but is further cleaved into angiotensin II catalyzed by the angiotensin-converting enzyme (ACE) released from the lungs. From the C-terminal of the decapeptide, a dipeptide is released leaving the octapeptide angiotensin II which is the biologically active hormone that exerts its effect on blood vessels. It acts as vasoconstriction causing constriction of the blood vessels and because of that blood pressure increases.

Functions of  Angiotensin II

Angiotensin II acts as a Na/H exchanger in the proximal tubules of the kidney and promotes reabsorption of the Na and H excretion. Proton excretion is coupled with the reabsorption of bicarbonate ions. Therefore, angiotensin-converting enzyme, or ACE is a good target for antihypertensive agents.

It also stimulates the release of antidiuretic hormone (or vasopressin) from the pituitary gland which causes water retention, the release of adrenaline and aldosterone from the adrenal gland, and the release of noradrenaline from the central nervous system. The release of adrenalin and noradrenalin promotes vasoconstriction while aldosterone influences the filtration of the kidneys. However, it can be further cleaved to angiotensin III and IV, catalyzed by aminopeptidase A and N respectively but these end products are not as important as angiotensin II.

Treatment of angiotensin II-induced hypertension

As angiotensin II is a vasoconstrictor, it increases blood pressure resulting in a serious health problem called hypertension. It is recognized by specific cell surface receptors and by targeting these receptors, hypertension induced by it can be treated. To treat patients with this type of hypertension, angiotensin II receptor blockers such as Azilsartan, candesartan, eprosartan, losartan, and olmesartan can be used.

Alternatively, this type of hypertension can also be treated by inhibiting the key enzyme the angiotensin-converting enzyme by using some chemicals. These chemicals are called angiotensin-converting enzyme inhibitors (or ACE inhibitors) and these are benazepril, captopril, enalapril, and fosinopril that can inhibit the angiotensin-converting enzyme and thus prevent the production of angiotensin II.

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