Angiotensinogen Angiotensin Metabolic Pathway

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(Last Updated On: April 23, 2017)
Step wise illustration of formation of different types of angiotensin from precursor protein angiotensinogen

Stepwise illustration of the formation of different types of angiotensin from the 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.

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

Angiotensin I has no biological activity but is further cleaved into the 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 a 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 the antihypertensive agents.

It also stimulates the release of antidiuretic hormone (or vasopressin) from the pituitary gland that causes water retention, the release of adrenaline and aldosterone from the adrenal gland and release of noradrenaline from the central nervous system. The release of adrenalin and noradrenalin promotes the 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 that important as angiotensin II.

Treatment of angiotensin II-induced hypertension

As angiotensin II is a vasoconstrictor, it increases the blood pressure resulting into a serious health problem called as hypertension. It is recognized by specific cell surface receptors and targeting these receptors, hypertension induced by it can be treated. To treat patients with this type of hypertension, angiotensin II receptor blocker such as Azilsartan, candesartan, eprosartan, losartan, 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 as angiotensin-converting enzyme inhibitor (or ACE inhibitor) 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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