Renin

Renin is an aspartyl protease enzyme produced by the juxtaglomerular cells of the kidney. It catalyzes the hydrolysis of angiotensinogen, a protein released by the liver, to form angiotensin I, the initial step in the renin-angiotensin-aldosterone system (RAAS) that regulates blood pressure and electrolyte balance.

Renin is synthesized as the inactive precursor prorenin in the granulated cells of the afferent arterioles and secreted into the bloodstream. Prorenin is activated to renin by proteolytic removal of the prosegment, though nonproteolytic activation via receptor interactions can also occur. Secreted renin is stored for rapid release in response to stimuli such as low blood pressure or reduced sodium delivery to the distal tubule.

Renin release is tightly regulated by several factors. Renal perfusion pressure, the delivery of sodium chloride to the macula densa, and sympathetic nervous system activity through beta-1 adrenergic receptors influence renin secretion. Additional local and systemic signals can modulate its production and release.

Functionally, renin initiates the RAAS cascade by producing angiotensin I, which is converted to angiotensin II by angiotensin-converting enzyme. Angiotensin II constricts blood vessels, stimulates aldosterone secretion, and promotes sodium and water reabsorption, collectively increasing blood pressure and maintaining circulatory homeostasis.

Clinical and therapeutic relevance: measurements of plasma renin activity or direct renin concentration aid in evaluating hypertension and certain mineralocorticoid disorders. Therapeutic strategies targeting the RAAS include ACE inhibitors, angiotensin receptor blockers, and direct renin inhibitors such as aliskiren.