Differential effects of eplerenone versus amlodipine on muscle metaboreflex function in hypertensive humans

Poghni A. Peri-Okonny, Alejandro Velasco, Hamza Lodhi, Zhongyun Wang, Debbie Arbique, Beverley A Huet, Gary Iwamoto, Jere H Mitchell, Masaki Mizuno, Scott Smith, Wanpen Vongpatanasin

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1706-1714
Number of pages9
JournalJournal of Clinical Hypertension
Volume23
Issue number9
DOIs
StatePublished - Sep 2021

Keywords

  • exercise
  • hypertension
  • metaboreflex
  • sympathetic nervous system

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Cardiology and Cardiovascular Medicine

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