期刊
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
卷 317, 期 4, 页码 R576-R587出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00174.2019
关键词
blood pressure; exercise; rats; transient receptor potential vanilloid-1
类别
资金
- National Institute of Arthritis and Muskuloskeletal and Skin Diseases [R01-AR-059397]
- National Heart, Lung, and Blood Institute [P01-HL-134609]
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 mu g/100 mu L), ruthenium red (100 mu g/100 mu L), or iodoresiniferatoxin (IRTX; 1 mu g/100 mu 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 alpha-beta-methylene ATP (10 mu 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.
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