Blocking the transient receptor potential vanilloid-1 does not reduce the exercise pressor reflex in healthy rats

Controversy exists regarding the role played by transient receptor potential vanilloid-1 (TRPV1) in evoking the exercise pressor reflex. Here, we determine the role played by TRPV1 in evoking this reflex while assessing possible confounding factors arising from TRPV1 antagonists or from the vehicle...

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Published in:American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2019-10, Vol.317 (4), p.R576-R587
Main Authors: Ducrocq, Guillaume P, Estrada, Juan A, Kim, Joyce S, Kaufman, Marc P
Format: Article
Language:English
Subjects:
Animals
Blood Pressure
Capsaicin - analogs & derivatives
Capsaicin - pharmacology
Diterpenes - pharmacology
Gene Expression Regulation - drug effects
Human health and pathology
Life Sciences
Male
Physical Conditioning, Animal
Rats
Rats, Sprague-Dawley
Reflex
Ruthenium Red - pharmacology
Sensory System Agents - pharmacology
Tissues and Organs
TRPV Cation Channels - antagonists & inhibitors
TRPV Cation Channels - metabolism
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Summary:Controversy exists regarding the role played by transient receptor potential vanilloid-1 (TRPV1) in evoking the exercise pressor reflex. Here, we determine the role played by TRPV1 in evoking this reflex while assessing possible confounding factors arising from TRPV1 antagonists or from the vehicle in which they were dissolved. The exercise pressor reflex was evoked in decerebrated, anesthetized Sprague-Dawley rats by electrical stimulation of the tibial nerve to contract the triceps surae muscles statically. This procedure was repeated before and after injection of the TRPV1 blockers: capsazepine (100 μg/100 μL), ruthenium red (100 μg/100 μL), or iodoresiniferatoxin (IRTX; 1 μg/100 μL). We found that capsazepine decreased the exercise pressor reflex when the drug was dissolved in DMSO (-10 ± 9 mmHg; = 0.015; = 7). However, similar reduction was found when DMSO alone was injected (-8 ± 5 mmHg; = 0.023; = 5). Capsazepine, dissolved in ethanol (2 ± 6 mmHg; = 0.49; = 7), ruthenium red (-4 ± 12 mmHg; = 0.41; = 7), or IRTX (4 ± 18 mmHg; = 0.56; = 7), did not significantly decrease the exercise pressor reflex. In addition, we found that capsazepine and ruthenium red had "off-target" effects. Capsazepine decreased the pressor response evoked by intra-arterial injection of bradykinin (500 ng/kg; -12 ± 13 mmHg; = 0.028; = 9) and α-β-methylene ATP (10 μg/kg; -7 ± 8 mmHg; = 0.019; = 10), whereas ruthenium red decreased the ability of the muscle to produce and sustain force (-99 ± 83 g; = 0.020; = 7). Our data therefore suggest that TRPV1 does not play a role in evoking the exercise pressor reflex. Additionally, given their strong off-target effects, capsazepine and ruthenium red should not be used for studying the role played by TRPV1 in evoking the exercise pressor reflex.
ISSN:0363-6119
1522-1490
DOI:10.1152/ajpregu.00174.2019