Journal article
The role of endothelin A receptors in peripheral vascular control at rest and during exercise in patients with hypertension
The Journal of physiology, Vol.598(1), pp.71-84
01/01/2020
DOI: 10.1113/JP279077
PMCID: PMC7986898
PMID: 31705661
Abstract
Exercise in patients with hypertension can be accompanied by an abnormal cardiovascular response that includes attenuated blood flow and an augmented pressor response. Endothelin-1, a very potent vasoconstrictor, is a key modulator of blood flow and pressure during in health and has been implicated as a potential cause of the dysfunction in hypertension. We assessed the role of endothelin-1, acting through endothelin A (ET
) receptors, in modulating the central and peripheral cardiovascular responses to exercise in patients with hypertension via local antagonism of these receptors during exercise. ET
receptor antagonism markedly increased leg blood flow, vascular conductance, oxygen delivery, and oxygen consumption during exercise; interestingly, these changes occurred in the presence of reduced leg perfusion pressure, indicating that these augmentations were driven by changes in vascular resistance. These data indicate that ET
receptor antagonism could be a viable therapeutic approach to improve blood flow during exercise in hypertension.
Patients with hypertension can exhibit impaired muscle blood flow and exaggerated increases in blood pressure during exercise. While endothelin (ET)-1 plays a role in regulating blood flow and pressure during exercise in health, little is known about the role of ET-1 in the cardiovascular response to exercise in hypertension. Therefore, eight volunteers diagnosed with hypertension were studied during exercise with either saline or BQ-123 (ET
receptor antagonist) infusion following a 2-week withdrawal of anti-hypertensive medications. The common femoral artery and vein were catheterized for drug infusion, blood collection and blood pressure measurements, and leg blood flow was measured by Doppler ultrasound. Patients exercised at both absolute (0, 5, 10, 15 W) and relative (40, 60, 80% peak power) intensities. BQ-123 increased blood flow at rest (79 ± 87 ml/min; P = 0.03) and augmented the exercise-induced hyperaemia at most intensities (80% saline: Δ3818±1222 vs. BQ-123: Δ4812±1469 ml/min; P = 0.001). BQ-123 reduced leg MAP at rest (-8 ± 4 mmHg; P < 0.001) and lower intensities (0-10 W; P < 0.05). Systemic diastolic blood pressure was reduced (0 W, 40%; P < 0.05), but systemic MAP was defended by an increased cardiac output. The exercise pressor response (ΔMAP) did not differ between conditions (80% saline: 25 ± 10, BQ-123: 30 ± 7 mmHg; P = 0.17). Thus, ET-1, acting through the ET
receptors, contributes to the control of blood pressure at rest and lower intensity exercise in these patients. Furthermore, the finding that ET-1 constrains the blood flow response to exercise suggests that ET
receptor antagonism could be a therapeutic approach to improve blood flow during exercise in hypertension.
Details
- Title: Subtitle
- The role of endothelin A receptors in peripheral vascular control at rest and during exercise in patients with hypertension
- Creators
- Jesse C Craig - University of UtahRyan M Broxterman - Geriatric Research Education and Clinical CenterD Taylor La Salle - University of UtahJames Cerbie - University of UtahStephen M Ratchford - University of UtahJayson R Gifford - University of UtahKanokwan Bunsawat - University of UtahAshley D Nelson - University of UtahAmber D Bledsoe - University of UtahDavid E Morgan - University of UtahD Walter Wray - University of UtahRussell S Richardson - University of UtahJoel D Trinity - University of Utah
- Resource Type
- Journal article
- Publication Details
- The Journal of physiology, Vol.598(1), pp.71-84
- DOI
- 10.1113/JP279077
- PMID
- 31705661
- PMCID
- PMC7986898
- NLM abbreviation
- J Physiol
- ISSN
- 0022-3751
- eISSN
- 1469-7793
- Grant note
- I21 RX001418 / RRD VA 2T32HL007576 / National Institutes of Health NRSA I01 RX001311 / RRD VA T32 HL007576 / NHLBI NIH HHS IK2 RX001215 / RRD VA T32 HL139451 / NHLBI NIH HHS R01 HL118313 / NHLBI NIH HHS 1T32HL139451 / NHLBI NIH HHS I01 RX001697 / RRD VA
- Language
- English
- Date published
- 01/01/2020
- Academic Unit
- Health, Sport, and Human Physiology
- Record Identifier
- 9984948044802771
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