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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]

PMID: 31365302

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Project description:Key pointsAlthough the exercise pressor reflex (EPR) and the chemoreflex (CR) are recognized for their sympathoexcitatory effect, the cardiovascular implication of their interaction remains elusive. We quantified the individual and interactive cardiovascular consequences of these reflexes during exercise and revealed various modes of interaction. The EPR and hypoxia-induced CR interaction is hyper-additive for blood pressure and heart rate (responses during co-activation of the two reflexes are greater than the summation of the responses evoked by each reflex) and hypo-additive for peripheral haemodynamics (responses during co-activation of the reflexes are smaller than the summated responses). The EPR and hypercapnia-induced CR interaction results in a simple addition of the individual responses to each reflex (i.e. additive interaction). Collectively, EPR:CR co-activation results in significant cardiovascular interactions with restriction in peripheral haemodynamics, resulting from the EPR:CR interaction in hypoxia, likely having the most crucial impact on the functional capacity of an exercising human.AbstractWe investigated the interactive effect of the exercise pressor reflex (EPR) and the chemoreflex (CR) on the cardiovascular response to exercise. Eleven healthy participants (5 females) completed a total of six bouts of single-leg knee-extension exercise (60% peak work rate, 4 min each) either with or without lumbar intrathecal fentanyl to attenuate group III/IV afferent feedback from lower limbs to modify the EPR, while breathing either ambient air, normocapnic hypoxia (Sa O2 ∼79%, Pa O2 ∼43 mmHg, Pa CO2 ∼33 mmHg, pH ∼7.39), or normoxic hypercapnia (Sa O2 ∼98%, Pa O2 ∼105 mmHg, Pa CO2 ∼50 mmHg, pH ∼7.26) to modify the CR. During co-activation of the EPR and the hypoxia-induced CR (O2 -CR), mean arterial pressure and heart rate were significantly greater, whereas leg blood flow and leg vascular conductance were significantly lower than the summation of the responses evoked by each reflex alone. During co-activation of the EPR and the hypercapnia-induced CR (CO2 -CR), the haemodynamic responses were not different from the summated responses to each reflex response alone (P ≥ 0.1). Therefore, while the interaction resulting from the EPR:O2 -CR co-activation is hyper-additive for blood pressure and heart rate, and hypo-additive for peripheral haemodynamics, the interaction resulting from the EPR:CO2 -CR co-activation is simply additive for all cardiovascular parameters. Thus, EPR:CR co-activation results in significant interactions between cardiovascular reflexes, with the impact differing when the CR activation is achieved by hypoxia or hypercapnia. Since the EPR:CR co-activation with hypoxia potentiates the pressor response and restricts blood flow to contracting muscles, this interaction entails the most functional impact on an exercising human.

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Dataset Information

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

Publications

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

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