TY - JOUR
T1 - Differential effects of eplerenone versus amlodipine on muscle metaboreflex function in hypertensive humans
AU - Peri-Okonny, Poghni A.
AU - Velasco, Alejandro
AU - Lodhi, Hamza
AU - Wang, Zhongyun
AU - Arbique, Debbie
AU - Adams-Huet, Beverley
AU - Iwamoto, Gary
AU - Mitchell, Jere H.
AU - Mizuno, Masaki
AU - Smith, Scott
AU - Vongpatanasin, Wanpen
N1 - Publisher Copyright:
© 2021 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC
PY - 2021/9
Y1 - 2021/9
N2 - Numerous studies have demonstrated that sympathetic nervous system overactivation during exercise in hypertensive rodents and humans is due, in part, to an exaggerated reflex response known as the exercise pressor reflex. Our prior studies have implicated a key role of mineralocorticoid receptor activation in mediating an augmented exercise pressor reflex in spontaneously hypertensive rats, which is mitigated by blockade with eplerenone. However, the effect of eplerenone on exercise pressor reflex has not been assessed in human hypertension. Accordingly, the authors performed a randomized crossover study to compare the effects of eplerenone to another antihypertensive drug from a different class amlodipine on sympathetic nerve activity (SNA) in 14 patients with uncomplicated hypertension. The authors found that amlodipine unexpectedly augmented the increase in SNA during the second minute of isometric handgrip, which persisted into the post-exercise circulatory arrest period (∆ SNA, from rest of 15 ± 2 vs. 9 ± 2 vs. 10 ± 2 bursts/min, amlodipine vs. baseline vs. eplerenone, respectively, p <.01), suggesting an exaggerated muscle metaboreflex function. Eplerenone did not alter sympathetic responses to exercise or post-exercise circulatory arrest in the same hypertensive individuals. In conclusions, our studies provide the first direct evidence for a potentially unfavorable potentiation of muscle metaboreflex by amlodipine during isometric handgrip exercise in hypertensive patients whereas eplerenone has no significant effect. Our study may have clinical implications in terms of selection of antihypertensive agents that have the least detrimental effects on sympathetic neural responses to isometric exercise.
AB - Numerous studies have demonstrated that sympathetic nervous system overactivation during exercise in hypertensive rodents and humans is due, in part, to an exaggerated reflex response known as the exercise pressor reflex. Our prior studies have implicated a key role of mineralocorticoid receptor activation in mediating an augmented exercise pressor reflex in spontaneously hypertensive rats, which is mitigated by blockade with eplerenone. However, the effect of eplerenone on exercise pressor reflex has not been assessed in human hypertension. Accordingly, the authors performed a randomized crossover study to compare the effects of eplerenone to another antihypertensive drug from a different class amlodipine on sympathetic nerve activity (SNA) in 14 patients with uncomplicated hypertension. The authors found that amlodipine unexpectedly augmented the increase in SNA during the second minute of isometric handgrip, which persisted into the post-exercise circulatory arrest period (∆ SNA, from rest of 15 ± 2 vs. 9 ± 2 vs. 10 ± 2 bursts/min, amlodipine vs. baseline vs. eplerenone, respectively, p <.01), suggesting an exaggerated muscle metaboreflex function. Eplerenone did not alter sympathetic responses to exercise or post-exercise circulatory arrest in the same hypertensive individuals. In conclusions, our studies provide the first direct evidence for a potentially unfavorable potentiation of muscle metaboreflex by amlodipine during isometric handgrip exercise in hypertensive patients whereas eplerenone has no significant effect. Our study may have clinical implications in terms of selection of antihypertensive agents that have the least detrimental effects on sympathetic neural responses to isometric exercise.
KW - exercise
KW - hypertension
KW - metaboreflex
KW - sympathetic nervous system
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U2 - 10.1111/jch.14333
DO - 10.1111/jch.14333
M3 - Article
C2 - 34432358
AN - SCOPUS:85113285418
SN - 1524-6175
VL - 23
SP - 1706
EP - 1714
JO - Journal of Clinical Hypertension
JF - Journal of Clinical Hypertension
IS - 9
ER -