Functional knockout of the TRPV1 channel has no effect on the exercise pressor reflex in rats
The role played by the transient receptor potential vanilloid 1 (TRPV1) channel on the thin fibre afferents evoking the exercise pressor reflex is controversial. To shed light on this controversy, we compared the exercise pressor reflex between newly developed TRPV1+/+, TRPV1+/− and TRPV1−/− rats. C...
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| Published in: | The Journal of physiology Vol. 601; no. 23; pp. 5241 - 5256 |
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| Main Authors: | , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
London
Wiley Subscription Services, Inc
01-12-2023
Wiley |
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| Online Access: | Get full text |
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| Summary: | The role played by the transient receptor potential vanilloid 1 (TRPV1) channel on the thin fibre afferents evoking the exercise pressor reflex is controversial. To shed light on this controversy, we compared the exercise pressor reflex between newly developed TRPV1+/+, TRPV1+/− and TRPV1−/− rats. Carotid arterial injection of capsaicin (0.5 μg), evoked significant pressor responses in TRPV1+/+ and TRPV1+/− rats, but not in TRPV1−/− rats. In acutely isolated dorsal root ganglion neurons innervating the gastrocnemius muscles, capsaicin evoked inward currents in neurons isolated from TRPV1+/+ and TRPV1+/− rats but not in neurons isolated from TRPV1−/− rats. The reflex was evoked by stimulating the tibial nerve in decerebrated rats whose femoral artery was either freely perfused or occluded. We found no difference between the reflex in the three groups of rats regardless of the patency of the femoral artery. For example, the peak pressor responses to contraction in TRPV1+/+, TRPV1+/− and TRPV1−/− rats with patent femoral arteries averaged 17.1 ± 7.2, 18.9 ± 12.4 and 18.4 ± 8.6 mmHg, respectively. Stimulation of the tibial nerve after paralysis with pancuronium had no effect on arterial pressure, findings which indicated that the pressor responses to contraction were not caused by electrical stimulation of afferent tibial nerve axons. We also found that expression levels of acid‐sensing ion channel 1 and endoperoxide 4 receptor in the L4 and 5 dorsal root ganglia were not upregulated in the TRPV1−/− rats. We conclude that TRPV1 is not needed to evoke the exercise pressor reflex in rats whose contracting muscles have either a patent or an occluded arterial blood supply.
Key points
A reflex arising in contracting skeletal muscle contributes to the increases in arterial blood pressure, cardiac output and breathing evoked by exercise.
The sensory arm of the reflex comprises both mechanoreceptors and metaboreceptors, of which the latter signals that blood flow to exercising muscle is not meeting its metabolic demand.
The nature of the channel on the metaboreceptor sensing a mismatch between supply and demand is controversial; some believe that it is the transient receptor potential vanilloid 1 (TRPV1) channel.
Using genetically engineered rats in which the TRPV1 channel is rendered non‐functional, we have shown that it is not needed to evoke the metaboreflex.
figure legend In decerebrated rats, CRISPR‐induced functional knockout of TRPV1 channels had no effect on the magnitude of either the exercise pressor reflex evoked by static contraction of the triceps surae muscles or the muscle mechanoreflex evoked by calcaneal tendon stretch. Evidence of functional TRPV1 channel knockout was provided in vitro by showing that capsaicin, a TRPV1 agonist, evoked inward currents in TRPV+/+ and TRPV1+/− dorsal root ganglion neurons innervating the triceps surae muscles, but did not evoke inward currents in their TRPV1−/− counterparts. Evidence of functional TRPV1 channel knockout in vivo was provided by showing that capsaicin, injected into the systemic circulation, evoked pressor responses in TRPV1+/+ and TRPV1+/− rats but did not evoke pressor responses in TRPV1−/− rats. |
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| Bibliography: | The peer review history is available in the Supporting information section of this article Handling Editors: Harold Schultz & Igor Fernandes https://doi.org/10.1113/JP285267#support‐information‐section . ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 0022-3751 1469-7793 |
| DOI: | 10.1113/JP285267 |