Angiotensin II is a hormone that plays an important role in regulating blood pressure and fluid balance in the body. It is part of the renin-angiotensin-aldosterone system (RAAS) which controls blood pressure through a variety of mechanisms. Understanding what stimulates the release of angiotensin II provides insight into how the RAAS maintains normal blood pressure and fluid homeostasis.
Overview of the Renin-Angiotensin-Aldosterone System
The RAAS is activated when the body senses a need to increase blood pressure or retain more fluid. This begins with the release of the enzyme renin from the kidneys when blood pressure or fluid volume become too low. Renin then cleaves angiotensinogen, which is produced in the liver, into angiotensin I. Angiotensin I is inactive, but is subsequently converted into angiotensin II by angiotensin-converting enzyme (ACE) which is primarily located in the lungs. Angiotensin II is the major active hormone of the RAAS that has several important effects:
- Constricts blood vessels to increase blood pressure
- Stimulates the adrenal glands to release aldosterone, which promotes sodium and fluid retention by the kidneys to increase blood volume
- Acts on the brain to increase water intake and constrict blood vessels
- Promotes the release of vasopressin from the pituitary gland to enhance water reabsorption by the kidneys
Overall, these actions of angiotensin II serve to increase blood pressure both by constricting blood vessels and increasing fluid volume. Therefore, understanding what stimulates renin release to initiate this cascade and produce angiotensin II provides insight into blood pressure regulation.
Decreased Blood Pressure Stimulates Renin Release
One of the most potent stimuli for renin release from the kidneys is a direct decrease in blood pressure. This is sensed by the juxtaglomerular cells in the kidneys which produce renin. These specialized cells are located near the afferent arterioles that bring blood into the glomeruli of the kidneys for filtration. When blood pressure in these arterioles drops, it triggers juxtaglomerular cells to secrete renin into the circulation.
Some causes of decreased blood pressure that can stimulate renin release include:
- Blood loss or hemorrhage
- Fluid loss from vomiting, diarrhea, or diuretic use
- Vasodilation from medications or autonomic dysfunction
- Heart failure
- Liver cirrhosis
In each case, mean arterial pressure declines which is sensed by the juxtaglomerular apparatus and leads to increased renin secretion. This initiates the RAAS cascade to generate angiotensin II and attempt to restore normal blood pressure.
Decreased Sodium Delivery to the Distal Nephron Stimulates Renin
The macula densa cells of the kidneys also regulate renin release in response to signals of decreased fluid volume. The macula densa are specialized cells that sense the concentration of sodium chloride in the tubular fluid of the distal nephron. A decreased delivery of sodium to this region, indicating low fluid volume, triggers the macula densa cells to signal for increased renin release.
Conditions that can decrease sodium delivery to the distal nephron and macula densa include:
- Volume depletion
- Diuretic use
- Renal artery stenosis
- Low-salt diet
The low sodium sensed at the macula densa indicates a need for increased sodium and fluid retention. This stimulates renin release to initiate the RAAS system and increase fluid volume through the actions of aldosterone.
Sympathetic Nervous System Activation Stimulates Renin
The sympathetic nervous system also regulates renin release, providing a link between cardiovascular control centers in the brain and the kidneys. Increased sympathetic activity triggered by hypotension or hypovolemia causes direct stimulation of β-adrenergic receptors on the juxtaglomerular cells of the kidneys. This leads to increased production and secretion of renin.
Some examples where sympathetic activation increases renin release include:
- Hemorrhage
- Congestive heart failure
- Cirrhosis
- Sodium depletion
The sympathetic stimulation serves to activate the RAAS system including increased angiotensin II production to respond to the low blood pressure or volume depletion state.
Other Factors That Stimulate Renin Release
In addition to the major stimuli of decreased blood pressure, low sodium delivery to the distal nephron, and increased sympathetic activity, some other factors can also influence renin release:
- Decreased oxygen tension – Renin release is increased by hypoxia at the juxtaglomerular cells.
- Increased prostaglandins – Prostaglandins can directly stimulate renin release from juxtaglomerular cells.
- Decreased calcium – A decrease in intracellular calcium concentration in juxtaglomerular cells stimulates renin secretion.
- Certain drugs – Some medications including ACE inhibitors, diuretics, and beta-blockers can alter renin release as side effects.
However, the predominant stimuli for renin release remain blood pressure, distal sodium delivery, and sympathetic nerve activity.
Negative Feedback by Angiotensin II
Interestingly, angiotensin II itself serves as a negative feedback signal to inhibit further renin release. Angiotensin II acts on the juxtaglomerular cells to decrease renin secretion after the RAAS has been activated and blood pressure increases. This prevents uncontrolled increases in angiotensin II production.
Therefore, the major stimuli for renin release are countered by angiotensin II negative feedback once RAAS activation has occurred. This system allows precise control of blood pressure and sodium balance through regulated renin and subsequent angiotensin II generation.
Summary of Stimuli for Renin and Angiotensin II Release
In summary, the major stimuli that promote renin release and subsequent generation of angiotensin II are:
- Decreased arterial blood pressure
- Decreased sodium delivery to distal nephron (detected by macula densa)
- Increased sympathetic nervous system activity
These stimuli indicate a need for increased fluid retention and blood pressure via RAAS activation. Angiotensin II then counterbalances its own production through negative feedback on renin release.
Conclusion
Regulated release of renin is the first step in generating the active hormone angiotensin II. The key stimuli for renin secretion are decreased blood pressure, decreased distal sodium delivery, and increased sympathetic tone. These signals indicate depletion of blood volume or need to retain fluid. Angiotensin II is then produced to correct this by constricting blood vessels and stimulating sodium retention. Fine control of renin release allows precise regulation of angiotensin II levels to maintain blood pressure and fluid homeostasis.