Renin
Also known as: angiotensinogenase
A proteolytic enzyme (not a classical hormone) secreted by the juxtaglomerular cells of the kidney when renal perfusion or sodium falls; it cleaves angiotensinogen to angiotensin I — the rate-limiting step of the renin–angiotensin–aldosterone system.
Overview
Renin is an aspartyl protease stored in granules of the juxtaglomerular (granular) cells, modified smooth-muscle cells in the wall of the afferent arteriole at the vascular pole of the glomerulus. Its only known substrate is angiotensinogen, an α2-globulin made continuously by the liver; renin removes its N-terminal decapeptide, angiotensin I, which is converted to the active angiotensin II by angiotensin-converting enzyme. Because angiotensinogen is abundant, renin secretion sets the rate of the whole cascade.
Three signals control secretion: (1) an intrarenal baroreceptor — reduced stretch of the afferent arteriole increases release; (2) the macula densa — reduced NaCl delivery to the distal tubule increases release (via prostaglandin E₂ and nitric oxide); (3) sympathetic β1-adrenergic stimulation of the granular cells. Angiotensin II (short-loop feedback), ANP and high pressure inhibit release.
- Location
Source: juxtaglomerular cells of the afferent arteriole (juxtaglomerular apparatus). Substrate: plasma angiotensinogen (from the liver).
Function
- Cleaves angiotensinogen to angiotensin I, initiating the RAAS.
- Thereby defends blood pressure, extracellular volume and GFR.
- Physiology
Class: glycoprotein enzyme (aspartyl protease); derived from prorenin. Acts in plasma, not on a receptor (a (pro)renin receptor exists but its role is uncertain).
- Regulation
Stimulated by reduced renal perfusion pressure, low distal NaCl (macula densa), β1 sympathetic activity, loop diuretics and prostaglandins. Inhibited by angiotensin II, ANP, high NaCl, β-blockers and NSAIDs.
Clinical significance
Renovascular hypertension
Renal artery stenosis (atherosclerosis in older patients, fibromuscular dysplasia in young women) reduces perfusion → high renin and angiotensin II → hypertension with secondary hyperaldosteronism and hypokalaemia; ACE inhibitors may precipitate acute kidney injury in bilateral disease.
Aldosterone:renin ratio
Plasma renin is suppressed in primary hyperaldosteronism and raised in secondary hyperaldosteronism; the ratio is the screening test for primary aldosteronism. Aliskiren is a direct renin inhibitor.
Test yourself
A 45-year-old has hypertension, serum K⁺ 2.9 mmol/L, metabolic alkalosis and a very low plasma renin. Which is the most likely diagnosis?
- Renal artery stenosis
- Primary hyperaldosteronism
- Addison disease
- Phaeochromocytoma
Answer: Primary hyperaldosteronism
Autonomous aldosterone (Conn syndrome or bilateral adrenal hyperplasia) retains Na⁺ and wastes K⁺ and H⁺, and the expanded volume suppresses renin — a high aldosterone:renin ratio. Renal artery stenosis causes secondary hyperaldosteronism with high renin.
Compiled from standard anatomy and physiology references — see the Endocrine System sources. For education only; not medical advice.