TRPV1 Exaggerates Cardiovascular Responses to Physical Exercise in Normotensive but Not in Hypertensive Rats
Authors: Kunstetter Ana Cancado , Damasceno William Coutinho , Pires Washington , Soares Danusa Dias , Wanner Samuel Penna 
Published: June 2021

Introduction

The transient receptor potential vanilloid‐1 (TRPV1) is an ion channel involved in several physiological responses, including arterial pressure regulation. This channel seems to have an important role in endothelium‐dependent and ‐independent vasodilation. In spontaneously hypertensive rats (SHRs), chronic treatment with a TRPV1 agonist decreases mean arterial pressure, which makes the TRPV1 a potential target for hypertension treatment. We have already shown that in normotensive rats, the acute blockage of TRPV1 channels leads to an exaggerated increase in mean arterial pressure and heart rate during physical exercise. Therefore, in this study we investigated whether the role of TRPV1 channels in cardiovascular responses during physical exercise is affected by arterial hypertension.

Methods

Male Wistar normotensive and Wistar‐Kyoto SHRs (16–19 wk) were implanted with an intra‐arterial (ascending aorta) catheter to measure arterial pressure. The rats received an intra‐arterial injection of a TRPV1 antagonist N‐(4‐[6‐(4‐trifluoromethyl‐phenyl)‐pyrimidin‐4‐yloxy]‐benzothiazol‐2‐yl)‐acetamide (AMG 517, 60 μg/kg) or vehicle (20% ethanol in saline) and then were subjected to an incremental‐speed treadmill running at 24°C until fatigue. The pulsatile arterial pressure (which allowed the determination of mean, systolic and diastolic arterial pressures and the heart rate) was measured throughout the exercise period.

Results

In both normotensive rats and SHR, the incremental exercise increased mean, systolic and diastolic arterial pressures and the heart rate (for mean arterial pressure, fatigue: Normotensive: 126 ± 3 mmHg; SHR: 165 ± 4 mmHg versus beginning of exercise: Normotensive: 108 ± 4 mmHg; SHR: 158 ± 5 mmHg). As expected, in the normotensive rats, the AMG 517 led to a greater exercise‐induced increases in the mean, systolic and diastolic arterial pressures and in the heart rate. In contrast, the TRPV1 antagonist had no effect on any of the cardiovascular variables evaluated in the SHRs (for mean arterial pressure, min 19: AMG 517: 161 ± 5 mmHg; Vehicle 164 ± 4 mmHg). The changes (values at fatigue minus values at the beginning of exercise) in the mean arterial pressure (Normotensive: 20.1 ± 1.8 mmHg versus SHR 10.5 ± 3.3 mmHg; p < 0.05) as well as in the heart rate (Normotensive: 196 ± 13 bpm versus SHR: 149 ± 9 bpm, p < 0.05) were greater in normotensive rats than in SHRs when the incremental exercise was performed after the TRPV1 antagonist injection.

Conclusions

Despite inducing marked alterations in blood pressure regulation in the normotensive rats, the TRPV1 antagonist injection did not modify the cardiovascular responses to exercise in the SHRs, which suggests that the arterial hypertension affects the TRPV1‐mediated mechanism involved in arterial pressure regulation during exercise.

Support or Funding Information

CAPES, CNPq and FAPEMIG.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.