Related Experiment Video
Updated: Jun 17, 2026
05:13
A Rat Model of Central Fatigue Using a Modified Multiple Platform Method
Published on: August 14, 2018
Central fatigue induced by losartan involves brain serotonin and dopamine content
Laura H R Leite1, Alex G Rodrigues, Danusa D Soares
1Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Brazil.
Medicine and Science in Sports and Exercise
|January 14, 2010
Summary
Blocking angiotensin II (Ang II) AT1 receptors with losartan increases serotonin (5-HT) in the brain, leading to quicker central fatigue and higher body temperature during exercise in rats.
Area of Science:
- Neuroscience
- Exercise Physiology
- Cardiovascular Research
Background:
- Central fatigue during exercise is influenced by neurotransmitters like serotonin (5-HT) and dopamine (DA).
- The renin-angiotensin system, particularly angiotensin II (Ang II) acting on AT1 receptors, plays a role in physiological regulation.
- Understanding the interplay between Ang II and central neurotransmitter systems is crucial for comprehending exercise-induced fatigue.
Purpose of the Study:
- To investigate how blocking angiotensin II (Ang II) AT1 receptors affects central fatigue.
- To examine the influence of this blockade on brain serotonin (5-HT) and dopamine (DA) levels during exercise.
Main Methods:
- Rats received intracerebroventricular injections of losartan (Los) before a running exercise protocol until fatigue.
- Brain tissue from specific regions (preoptic area, hypothalamus, hippocampus, frontal cortex) was analyzed for 5-HT and DA levels using high-pressure liquid chromatography.
- Correlations between neurotransmitter levels, body heating rate, and time to fatigue were assessed.
Main Results:
- Losartan administration increased 5-HT content in the preoptic area and hypothalamus, correlating positively with body heating rate and inversely with time to fatigue.
- Reduced hippocampal 5-HT levels in losartan-treated rats were directly correlated with increased time to fatigue.
- While DA levels remained unaffected, a higher hypothalamic 5-HT/DA ratio was observed, correlating with increased body heating and reduced exercise duration.
Conclusions:
- Central fatigue induced by Ang II AT1 receptor blockade in exercising rats is linked to elevated 5-HT in the preoptic area/hypothalamus and decreased 5-HT in the hippocampus.
- The interaction between 5-HT and DA in the hypothalamus appears to contribute to hyperthermia and premature central fatigue following angiotensinergic inhibition.
Related Concept Videos
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
01:22Heart Failure Drugs: Diuretics
Heart failure and kidney perfusion are interconnected in a complex way. Reduced renal perfusion and venous congestion are two significant factors that contribute to renal dysfunction in heart failure. The kidneys, primarily responsible for fluid balance in the body, are adversely affected due to compromised cardiac output and increased venous pressure. In response to reduced renal perfusion, the kidneys activate neurohumoral mechanisms to restore balance. However, these mechanisms can be...
01:30Antihypertensive Drugs: Angiotensin II Receptor Blockers
In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...
01:29Heart Failure II: Pathophysiology
Systolic Heart Failure and Compensatory MechanismsSystolic heart failure (also termed HFrEF, Heart Failure with Reduced Ejection Fraction) is the most prevalent type of heart filure. It results in a decreased volume of blood being pumped from the ventricle. The aortic arch and carotid sinuses have baroreceptors that detect reduced blood pressure, triggering the sympathetic nervous system (SNS) to release epinephrine and norepinephrine. Initially, this response aims to boost heart rate and...
01:17Pathophysiology of Heart Failure
Heart failure (HF) is a progressive syndrome involving ventricles that leads to inadequate cardiac output. It can be classified based on location and output or ejection fraction. Ejection fraction (EF) is an essential measurement in the diagnosis and surveillance of HF. Reduced EF corresponds to systolic heart failure (HFrEF). However, HF with preserved ejection fraction (HFpEF) is becoming increasingly prevalent. Also known as diastolic HF, this form of HF is related to aging. The...
01:28Antihypertensive Drugs: Potassium-Sparing Diuretics
Liddle syndrome is a genetically inherited form of hypertension characterized by the overactivity of epithelial sodium channels in the nephron, the functional unit of the kidney. This heightened activity leads to increased sodium reabsorption and excessive excretion of potassium. To counteract this, potassium-sparing diuretics such as amiloride are used. They function by blocking these sodium channels, thereby reducing the influx of sodium into the epithelial cells and minimizing the loss of...