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 340 amino acids and has a mass of 37 kDa.
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).
Angiotensin I is further cleaved in the lungs by endothelial-bound angiotensin-converting enzyme (ACE) into angiotensin II, the most vasoactive peptide. 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. The heart, trying to overcome this increase in its 'load', works more vigorously, causing the blood pressure to rise. Angiotensin II also acts on the adrenal glands and releases aldosterone, 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 stimulating thirst, as well as conserving blood volume, by reducing urinary loss through the secretion of vasopressin from the posterior pituitary gland.
The normal concentration of renin in adult human plasma is 1.98-24.6 ng/L in the upright position.
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 the macula densa. The macula densa sense changes in volume delivery to the distal tubule, and responds to a drop in tubular volume 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 through beta-1 adrenoceptor activation.
Renin can bind to ATP6AP2, which results in a fourfold increase in the conversion of angiotensinogen to angiotensin I over that shown by soluble renin. In addition, renin binding results in phosphorylation of serine and tyrosine residues of ATP6AP2.
The gene for renin, REN, spans 12 kb of DNA and contains 8 introns. It produces several mRNA that encode different REN isoforms.
Mutations in the REN gene can be inherited, and are a cause of a rare inherited kidney disease. This disease is autosomal dominant*, meaning that it is characterized by a 50% chance of inheritance and slowly progressive chronic kidney disease that leads to the need for dialysis or a kidney transplant. Many – but not all – patients and families with this disease suffer from 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 40's while others may not go on dialysis until into their 70’s. This is a rare inherited kidney disease that exists in less than 1% of people with kidney disease.
Model organisms have been used in the study of REN function. A knockout mouse line, called Ren1Ren-1c Enhancer KO was generated. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty four tests were carried out on mutant mice and two significant abnormalities were observed. Homozygous mutant animals had a decreased heart rate and an increased susceptibility to bacterial infection. A more detailed analysis of this line indicated plasma creatinine was also increased and males had lower mean arterial pressure than controls.
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.
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. A PRA measurement may be compared to a plasma aldosterone concentration (PAC) as a PAC/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. ISBN1-4160-2328-3.
^Adams DJ, Beveridge DJ, van der Weyden L, Mangs H, Leedman PJ, Morris BJ (Nov 2003). "HADHB, HuR, and CP1 bind to the distal 3'-untranslated region of human renin mRNA and differentially modulate renin expression". The Journal of Biological Chemistry278 (45): 44894–903. doi:10.1074/jbc.M307782200. PMID12933794.
^ abAdams DJ, Head GA, Markus MA, Lovicu FJ, van der Weyden L, Köntgen F et al. (Oct 2006). "Renin enhancer is critical for control of renin gene expression and cardiovascular function". The Journal of Biological Chemistry281 (42): 31753–61. doi:10.1074/jbc.M605720200. PMID16895910.
^Ram CV (Sep 2009). "Direct inhibition of renin: a physiological approach to treat hypertension and cardiovascular disease". Future Cardiology5 (5): 453–65. 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 Pathology19 (1): 93–8. doi:10.1177/1066896908329413. PMID19098017.
^Hamilton Regional Laboratory Medicine Program - Laboratory Reference Centre Manual. Renin Direct.
^Phillips MI, Schmidt-Ott KM (Dec 1999). "The Discovery of Renin 100 Years Ago". News in Physiological Sciences14: 271–274. PMID11390864.
^Tigerstedt R, Bergman PG (1898). "Niere und Kreislauf" [Scandinavian Archives of Physiology]. Skandinavisches Archiv für Physiologie (in German) 8: 223–271. doi:10.1111/j.1748-1716.1898.tb00272.x.