Renin

Renin (

The enzyme renin is secreted by pericytes in the vicinity of the afferent arterioles and similar microvessels of the kidney from specialized cells of the juxtaglomerular apparatus—the juxtaglomerular cells, in response to three stimuli:

1. A decrease in arterial blood pressure (that could be related to a decrease in blood volume) as detected by
   baroreceptors
   (pressure-sensitive cells). This is the most direct causal link between blood pressure and renin secretion (the other two methods operate via longer pathways).
2. A decrease in sodium load delivered to the distal tubule. This load is measured by the macula densa of the juxtaglomerular apparatus.
3. β₁ adrenergic receptors
   .

Human renin is secreted by at least 2 cellular pathways: a constitutive pathway for the secretion of the precursor prorenin and a regulated pathway for the secretion of mature renin.^[6]

Renin–angiotensin system

The renin enzyme circulates in the bloodstream and

Angiotensin I is further cleaved in the lungs by endothelial-bound

The normal concentration of renin in adult human plasma is 1.98–24.6 ng/L in the upright position.^[10]

Function

Renin activates the

Renin secretion is also stimulated by sympathetic nervous stimulation, mainly through β₁ adrenoreceptor activation.^[12]

The (pro)renin receptor to which renin and prorenin bind is encoded by the gene ATP6ap2, ATPase H(+)-transporting lysosomal accessory protein 2, which results in a fourfold increase in the conversion of angiotensinogen to angiotensin I over that shown by soluble renin as well as non-hydrolytic activation of prorenin via a conformational change in prorenin which exposes the catalytic site to angiotensinogen substrate. In addition, renin and prorenin binding results in phosphorylation of serine and tyrosine residues of ATP6AP2.^[13]

The level of renin mRNA appears to be modulated by the binding of

Mutations in the REN gene can be inherited, and are a cause of a rare inherited kidney disease, so far found to be present in only 2 families. This disease is autosomal dominant, meaning that it is characterized by a 50% chance of inheritance and is a slowly progressive chronic kidney disease that leads to the need for dialysis or kidney transplantation. Many—but not all—patients and families with this disease have an elevation in serum potassium and unexplained anemia relatively early in life. Patients with a mutation in this gene can have a variable rate of loss of kidney function, with some individuals going on dialysis in their 40s while others may not go on dialysis until into their 70s. This is a rare inherited kidney disease that exists in less than 1% of people with kidney disease.^[16]

Clinical applications

An over-active renin-angiotensin system leads to vasoconstriction and retention of

In current medical practice, the renin–angiotensin–aldosterone system's overactivity (and resultant hypertension) is more commonly reduced using either ACE inhibitors (such as ramipril and perindopril) or angiotensin II receptor blockers (ARBs, such as losartan, irbesartan or candesartan) rather than a direct oral renin inhibitor. ACE inhibitors or ARBs are also part of the standard treatment after a heart attack.

The

Renin is usually measured as the plasma renin activity (PRA). PRA is measured specially in case of certain diseases that present with hypertension or hypotension. PRA is also raised in certain tumors.^[20] A PRA measurement may be compared to a plasma aldosterone concentration (PAC) as a PAC/PRA ratio.

Discovery and naming

The name renin =

• Angiotensin-converting enzyme
• Plasma renin activity
• Renin inhibitor
• Renin stability regulatory element (REN-SRE)

References