Key result
Amlodipine unexpectedly augments post-exercise sympathetic nerve activity by ~50% versus eplerenone in hypertensive patients.
Why the study?
Mineralocorticoid receptor activation mediates an augmented exercise pressor reflex in hypertensive rats, but the effect of eplerenone had not been assessed in human hypertension.
Does eplerenone compared to amlodipine improve sympathetic nerve activity during isometric exercise in patients with uncomplicated hypertension?
RCT (n=14)
Single-blind
Randomized crossover
No
Does eplerenone compared to amlodipine improve sympathetic nerve activity during isometric exercise in patients with uncomplicated hypertension?
Absolute Event Rate: 10% vs 15%
p-value: p=<0.01
Amlodipine, but not eplerenone, unfavorably potentiates the muscle metaboreflex and sympathetic nerve activity during isometric exercise in hypertensive patients.
Amlodipine may potentiate sympathetic activity during exercise in hypertension; challenges CCB preference over MRAs and leaves open outcome trials.
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.
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Peri-Okonny et al. (2021) conducted an RCT in Essential hypertension (n=14). Eplerenone vs. Amlodipine (2.5-10 mg/day) and Baseline was evaluated on Change in sympathetic nerve activity (ΔSNA) from rest during post-exercise circulatory arrest (bursts/min) (p=<0.01). Amlodipine unexpectedly augmented the increase in sympathetic nerve activity during post-exercise circulatory arrest compared to eplerenone and baseline in hypertensive patients.
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