Angiotensinogen

Angiotensinogen is a protein that is created and released by the liver. A kidney enzyme, renin, breaks down this to form angiotensin I. Angiotensin II, an important precursor to this hormone, is not known to have any specific biological function in itself. Angiotensin II is metabolised by angiotensin-converting enzymes in the lungs and kidneys after it passes through the bloodstream.

1. Angiotensin-I (AI)

AI is produced from angiotensinogen through the action of renin. Renin is secreted by the kidneys and is responsible for regulating blood pressure. AI is converted into angiotensin II (AII), which binds to receptors on cells throughout the body. AII stimulates vasoconstriction, causing blood vessels to narrow. This leads to increased blood pressure.

2. Angiotensin II Receptor Antagonists (ARAs)

ARAs are drugs that block the effects of AII by binding to its receptor sites. ARAs have been used to treat hypertension and congestive heart failure. They may also improve insulin sensitivity.

3. Angiotensin Converting Enzyme Inhibitors (ACEIs)

ACEIs inhibit the conversion of AI to AII, thus, preventing the narrowing of blood vessels. 

Types of Angiotensin 

Angiotensin I

A reaction between angiotensinogen and renin produces angiotensin. Angiotensinogen forms decapeptide angiotensin I, which is formed by Renin’s cleavage of its peptide bonds. The macula densa increases renin.

• Through renal sympathetic stimulation, (90 mmHg systolic blood pressure), renal renin is released from the kidneys. 
• Interestingly, this specific sensing mechanism appears to activate renin secretion within macula densa. 
• When sodium salts were added to isolated preparations of the thick ascending limb with attached glomerulus, no effect was seen on renin secretion. 
• The chloride salts, however, may block renin secretion. 
• Studies and results obtained in vivo support the hypothesis that MD controls renin secretion through a change in sodium, potassium, and chloride transport rate mediated by a Na, K,2Cl cotransporter whose physiological activity is dependent upon the Cl concentration in the luminal compartment.

Angiotensin II

Vasopressin is produced by angiotensin II, a peptide that also inhibits vasodilatation by acting on smooth muscle. Additionally, angiotensin II stimulates aldosterone secretion, thereby, acting as an endocrine, autocrine/paracrine, and intracrine hormone.

• Angiotensin II production is decreased when ACE inhibitors inhibit ACE synthesis.
• Through an IP3-dependent mechanism, angiotensin II stimulates the release of calcium by smooth muscle cells and their contraction.
• In addition, angiotensin II is regarded as an adrenergic agonist that stimulates the reabsorption of sodium and the excretion of hydrogen, along with bicarbonate reabsorption.
• The end result is an increase in blood volume, pressure, and pH. Hence, ACE inhibitors are major antihypertensive medications.

Angiotensin III

In contrast to angiotensin II, angiotensin III produces 100% of aldosterone; it has 40% of vasopressor activity. 

• Activates the vasoconstriction process. Angiotensin II is converted into an amino peptide by aminopeptidase A.
• Natriuresis is triggered by AT2 receptor activation by angiotensin III but not by AT2 receptor activation via angiotensin II.
• Blocking the AT1 receptor causes the AT1 receptor to release angiotensin III, which leads to this natriuretic response.

Angiotensin IV

The hexapeptide angiotensin IV, like angiotensin III, is less active. The receptors for AT4 have not yet been identified precisely. C-Met receptors interact with angiotensin II via the HGF system. 

• The insulin-regulated aminopeptidase interacts with angiotensin IV in both systems.
• A possible function of AT4 is to regulate blood flow as well as memory.

The Renin-Angiotensin System

In addition to regulating arterial blood pressure and plasma sodium levels, the renin-angiotensin-aldosterone system (RAAS) is also involved in the regulation of blood vessels and the passage of calcium.

• Blood pressure is controlled and maintained by the renin-angiotensin system in the cells. This system automatically releases renin into the bloodstream whenever the blood pressure drops or rises.
• RENIN-ANGIOTENSIN is a system responsible for regulating and maintaining blood pressure. With an ACE inhibitor and receptor blocker, arterial blood pressure, blood volume, ventricular afterload, and ventricular preload may be reduced, as well as cardiac and vascular hypertrophy reversed.
• There are dual blockade approaches like combining Angiotensin II Receptor Blockers and Angiotensin Converter I and therapeutic modalities such as aliskiren, a recently approved hypertension treatment that inhibits renin directly.

The RAAS system and ACE inhibitors

A RAAS inhibitor interferes with the system by blocking ACE. Blood pressure is regulated by RAAS, which is a complex system. If the kidneys don’t produce enough renin, have low sodium levels, or have a high potassium level, one can be at risk for low blood volume and low salt levels. Angiotensinogen is the main substrate for renin, a substance synthesised in the liver.

• Angiotensinogen is present in the body and is cleaved by Renin and converted to angiotensin I. Angiotensin I is then changed over to angiotensin II by angiotensin-converting proteins.
• By engaging the muscles surrounding the veins, angiotensin II tightens veins and increases circulatory strain.
• Additionally, it stimulates the production of aldosterone, which enhances the reabsorption of salt and water and, consequently, increases pulse and blood volume.
• Blood vessels are dilated by ACE inhibitors by inhibiting angiotensin II production. A number of major organs are affected by ACE inhibitors, such as the kidney, blood vessels, heart, brain, and adrenal glands. 
• An inhibitory effect results in an increase in sodium and urine excretion, a decrease in resistance to blood flow in the kidneys, a boost in venous capacity, and a decrease in cardiac output, stroke work, and volume.

Conclusion

Angiotensin is responsible for controlling the pulse and fluid equilibrium in the human body. Angiotensin can also contract veins and cause various medical conditions. A typical treatment for angiotensin II is a medication that minimises blood pressure by keeping blood vessels open. Angiotensin II deficiency victims are provided with an estimation based on the severity of their condition.