From the Guidelines
The juxtaglomerular (JG) cells in the afferent arterioles of the kidney secrete renin in response to three main stimuli: decreased renal perfusion pressure, decreased sodium chloride delivery to the macula densa cells, and increased sympathetic nerve activity. These mechanisms work together as part of the renin-angiotensin-aldosterone system (RAAS), which helps regulate blood pressure and fluid balance, as described in a study published in Hypertension in 2023 1. The RAAS cascade is initiated in response to decreases in blood pressure, reductions in the delivery of sodium chloride to the macula densa of the distal convoluted tubule, and stimulation of renal sympathetic nerves. When the system is activated, renin is released from the kidneys and converts hepatic angiotensinogen to angiotensin I, which is then converted to angiotensin II, leading to vasoconstriction and aldosterone release, as also noted in a study published in the British Journal of Pharmacology in 2018 1. This system is crucial for maintaining homeostasis during conditions like hypovolemia, hemorrhage, or heart failure when blood pressure and renal perfusion are compromised. Some key points to consider include:
- Decreased renal perfusion pressure detected by baroreceptors in the afferent arteriole wall triggers renin release when blood pressure falls.
- Decreased sodium chloride delivery to the macula densa cells in the distal tubule stimulates renin secretion through tubuloglomerular feedback.
- Increased sympathetic nerve activity, particularly through beta-1 adrenergic receptors, promotes renin release. The most recent and highest quality study, published in 2023, provides the most relevant information on this topic, and its findings should be prioritized in clinical decision-making 1.
From the Research
Stimuli for Renin Secretion
The juxtaglomerular (JG) cells in the afferent arterioles of the kidney secrete renin in response to various stimuli, including:
- Decreased blood pressure and blood volume 2, 3, 4
- Increased sympathetic nerve activity 3, 4
- Macula densa signaling 3
- Stretch or mechanical pressure on the JG cells 2, 5, 4
- Changes in perfusion pressure in the afferent arterioles 2, 3, 4
- Arachidonic acid and its metabolic products 2
Mechanisms of Renin Release
The mechanisms of renin release involve:
- The renin baroreceptor, a nuclear mechanotransducer that transmits external forces to the chromatin to regulate Ren1 gene expression 3
- The myogenic response, where stretch activates the opening of stretch-sensitive Ca permeability channels that promote the influx of Ca to trigger active tension development 5
- The macula densa mechanism, where changes in sodium chloride concentration in the distal tubule trigger renin release 3
- Sympathetic nerve stimulation, which can modify renin release 3, 4
Role of Calcium and Arachidonic Acid
Calcium and arachidonic acid play important roles in the regulation of renin release: