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


ABSTRACT: 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 ?g/100 ?L), ruthenium red (100 ?g/100 ?L), or iodoresiniferatoxin (IRTX; 1 ?g/100 ?L). We found that capsazepine decreased the exercise pressor reflex when the drug was dissolved in DMSO (-10?±?9 mmHg; P = 0.015; n = 7). However, similar reduction was found when DMSO alone was injected (-8?±?5 mmHg; P = 0.023; n = 5). Capsazepine, dissolved in ethanol (2?±?6 mmHg; P = 0.49; n = 7), ruthenium red (-4?±?12 mmHg; P = 0.41; n = 7), or IRTX (4?±?18 mmHg; P = 0.56; n = 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; P = 0.028; n = 9) and ?-?-methylene ATP (10 ?g/kg; -7?±?8 mmHg; P = 0.019; n = 10), whereas ruthenium red decreased the ability of the muscle to produce and sustain force (-99?±?83 g; P = 0.020; n = 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.

SUBMITTER: Ducrocq GP 

PROVIDER: S-EPMC6842907 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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

Ducrocq Guillaume P GP   Estrada Juan A JA   Kim Joyce S JS   Kaufman Marc P MP  

American journal of physiology. Regulatory, integrative and comparative physiology 20190731 4


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 muscl  ...[more]

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