What are the main chemicals that signal the afferent arteriole to contract in tubuloglomerular (tubulo-glomerular) feedback?

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Last updated: March 15, 2025View editorial policy

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From the Research

The main chemicals that signal the afferent arteriole to contract during tubuloglomerular feedback are adenosine and angiotensin II. When the macula densa cells in the distal tubule detect increased sodium chloride concentration, they release adenosine, which acts directly on the afferent arteriole to cause vasoconstriction, as shown in a study published in 2009 1. Simultaneously, the juxtaglomerular cells release renin in response to these signals, which converts angiotensinogen to angiotensin I. Angiotensin I is then converted to angiotensin II by angiotensin-converting enzyme (ACE), and angiotensin II is a potent vasoconstrictor that further tightens the afferent arteriole, as demonstrated in a study from 2011 2. This dual chemical signaling system allows for precise regulation of glomerular filtration rate. The vasoconstriction reduces blood flow into the glomerulus, thereby decreasing filtration pressure and rate, which helps maintain homeostasis when the kidney detects excessive filtration. This negative feedback mechanism is crucial for maintaining appropriate salt and water balance in the body and protecting the kidney from pressure-induced damage, as discussed in a review from 2020 3. Additionally, studies have shown that adenosine A₁-receptor deficiency diminishes afferent arteriolar and blood pressure responses during nitric oxide inhibition and angiotensin II treatment 2, and that extravasal albumin concentration modulates contractile responses of renal afferent arterioles 4. However, the most recent and highest quality study on this topic is from 2020, which highlights the importance of angiotensin II in controlling glomerular filtration rate through its contractile effect on afferent and efferent arterioles 3. Some key points to consider include:

  • The role of adenosine in macula densa control of glomerular hemodynamics, as investigated in a study from 2002 5
  • The effect of increased extravasal albumin concentration on the vascular reactivity of renal afferent arterioles, as shown in a study from 2018 4
  • The potential contribution of these mechanisms to the control of extracellular fluid volume via adjustment of renal blood flow and glomerular filtration rate. Overall, adenosine and angiotensin II are the primary chemicals involved in signaling the afferent arteriole to contract during tubuloglomerular feedback, and their interaction is crucial for maintaining proper kidney function and overall health, as supported by the most recent and highest quality evidence from 2020 3.

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