Renin is not commonly referred to as ahormone, although it has a receptor, the (pro)renin receptor, also known as therenin receptor and prorenin receptor (see also below),[4] as well as enzymatic activity with which ithydrolyzesangiotensinogen toangiotensin I.
The primary structure of renin precursor consists of 406 amino acids with a pre- and a pro-segment carrying 20 and 46 amino acids, respectively. Mature renin contains 340amino acids and has a mass of 37kDa.[5]
A decrease in arterial blood pressure (that could be related to a decrease in blood volume) as detected bybaroreceptors (pressure-sensitive cells). This is the most direct causal link between blood pressure and renin secretion (the other two methods operate via longer pathways).
Human renin is secreted by at least 2 cellular pathways: a constitutive pathway for the secretion of the precursorprorenin and a regulated pathway for the secretion of mature renin.[6]
The renin enzyme circulates in the bloodstream andhydrolyzes (breaks down) angiotensinogen secreted from the liver into the peptideangiotensin I.
Angiotensin I is further cleaved in the lungs by endothelial-boundangiotensin-converting enzyme (ACE) intoangiotensin II, the most vasoactive peptide.[8][9] Angiotensin II is a potent constrictor of all blood vessels. It acts on the smooth muscle and, therefore, raises the resistance posed by these arteries to the heart, and so for the same cardiac output, the blood pressure will rise. Angiotensin II also acts on the adrenal glands and releasesaldosterone, which stimulates the epithelial cells in the distal tubule and collecting ducts of the kidneys to increase re-absorption of sodium, exchanging with potassium to maintain electrochemical neutrality, and water, leading to raised blood volume and raised blood pressure. The RAS also acts on the CNS to increase water intake by stimulatingthirst, as well as conserving blood volume, by reducing urinary loss through the secretion ofvasopressin from the posteriorpituitary gland.
The normal concentration of renin in adult humanplasma is 1.98–24.6 ng/L in the upright position.[10]
Renin activates therenin–angiotensin system by using its endopeptidase activity to cleave the peptide bonds between leucine and valine residues in angiotensinogen,[11] produced by theliver, to yieldangiotensin I, which is further converted intoangiotensin II byACE, the angiotensin–converting enzyme primarily within the capillaries of the lungs. Angiotensin II then constrictsblood vessels, increases the secretion ofADH andaldosterone, and stimulates thehypothalamus to activate the thirst reflex, each leading to an increase inblood pressure. Renin's primary function is therefore to eventually cause an increase in blood pressure, leading to restoration of perfusion pressure in the kidneys.
Renin is secreted from juxtaglomerular kidney cells, which sense changes in renal perfusion pressure, via stretch receptors in the vascular walls. The juxtaglomerular cells are also stimulated to release renin by signaling from themacula densa. The macula densa senses changes in sodium delivery to thedistal tubule, and responds to a drop in tubular sodium load by stimulating renin release in the juxtaglomerular cells. Together, the macula densa and juxtaglomerular cells comprise the juxtaglomerular complex.
Renin secretion is also stimulated by sympathetic nervous stimulation, mainly throughβ1 adrenoreceptor activation.[12]
The (pro)renin receptor to which renin and prorenin bind is encoded by the geneATP6ap2, 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 inphosphorylation of serine and tyrosine residues of ATP6AP2.[13]
Thegene for renin,REN, spans 12 kb of DNA and contains 8 introns.[15] It produces severalmRNA that encode different RENisoforms.
Mutations in theREN 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 isautosomal 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 fordialysis orkidney 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]
An over-active renin-angiotensin system leads to vasoconstriction and retention ofsodium and water. These effects lead tohypertension. Therefore,renin inhibitors can be used for the treatment of hypertension.[17][18] This is measured by theplasma renin activity (PRA).
In current medical practice, the renin–angiotensin–aldosterone system's overactivity (and resultant hypertension) is more commonly reduced using eitherACE inhibitors (such as ramipril and perindopril) orangiotensin 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.
Renin is usually measured as theplasma renin activity (PRA). PRA is measured specially in case of certain diseases that present withhypertension orhypotension. PRA is also raised in certain tumors.[20] A PRA measurement may be compared to a plasmaaldosterone concentration (PAC) as aPAC/PRA ratio.
^Boulpaep EL, Boron WF (2005). "Integration of Salt and Water Balance; The Adrenal Gland".Medical physiology: a cellular and molecular approach. St. Louis, MO: Elsevier Saunders. pp. 866–867, 1059.ISBN978-1-4160-2328-9.
^Kopp U, Aurell M, Nilsson IM, Ablad B (September 1980). "The role of beta-1-adrenoceptors in the renin release response to graded renal sympathetic nerve stimulation".Pflügers Archiv.387 (2):107–113.doi:10.1007/BF00584260.PMID6107894.S2CID25873845.
^Ram CV (Sep 2009). "Direct inhibition of renin: a physiological approach to treat hypertension and cardiovascular disease".Future Cardiology.5 (5):453–465.doi:10.2217/fca.09.31.PMID19715410.
^Méndez GP, Klock C, Nosé V (Feb 2011). "Juxtaglomerular cell tumor of the kidney: case report and differential diagnosis with emphasis on pathologic and cytopathologic features".International Journal of Surgical Pathology.19 (1):93–98.doi:10.1177/1066896908329413.PMID19098017.S2CID38702564.
^Hamilton Regional Laboratory Medicine Program - Laboratory Reference Centre Manual. Renin Direct.
^Tigerstedt R, Bergman PG (1898). "Niere und Kreislauf" [Kidney and Circulation].Skandinavisches Archiv für Physiologie (in German).8:223–271.doi:10.1111/j.1748-1716.1898.tb00272.x.
Kmoch S, Živná M, Bleyer AJ (2015)."Familial Juvenile Hyperuricemic Nephropathy Type 2". In Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJ, Gripp KW, Amemiya A (eds.).GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle. pp. 1993–2014.PMID21473025.
