Mineralocorticoid Receptor Activation Contributes to the Supine Hypertension of Autonomic Failure

Amy Arnold, Luis E. Okamoto, Alfredo Gamboa, Bonnie K. Black, Satish R. Raj, Fernando Elijovich, David Robertson, Cyndya A. Shibao, Italo Biaggioni

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Primary autonomic failure is characterized by disabling orthostatic hypotension, but at least half of these patients have paradoxical supine hypertension. Renin-angiotensin mechanisms were not initially thought to contribute to this hypertension because plasma renin activity is often undetectable in autonomic failure. Plasma aldosterone levels are normal, however, and we recently showed that plasma angiotensin II is elevated and acts at AT1 (angiotensin type 1) receptors to contribute to hypertension in these patients. Because aldosterone and angiotensin II can also bind mineralocorticoid receptors to elevate blood pressure, we hypothesized that mineralocorticoid receptor activation plays a role in the hypertension of autonomic failure. To test this hypothesis, we determined the acute effects of the mineralocorticoid receptor antagonist eplerenone (50 mg, oral) versus placebo on supine blood pressure in a randomized, double-blind, crossover study. Medications were given at 8:00 pm with blood pressure recorded every 2 hours for 12 hours. Ten primary autonomic failure patients with supine hypertension completed this study (7 pure autonomic failure, 2 multiple system atrophy, 1 parkinson's disease; 7 male; 70±2 years of age). Eplerenone maximally reduced supine systolic blood pressure by 32±6 mm Hg at 8 hours after administration (versus 8±10 mm Hg placebo, P=0.016), with no effect on nocturia (12-hour urine volume: 985±134 mL placebo versus 931±94 mL eplerenone, P=0.492; nocturnal weight loss:-1.19±0.15 kg placebo versus-1.18±0.15 kg eplerenone, P=0.766). These findings suggest that inappropriate mineralocorticoid receptor activation contributes to the hypertension of autonomic failure, likely independent of canonical mineralocorticoid effects, and provides rationale for use of eplerenone in these patients.

Original languageEnglish (US)
Pages (from-to)424-429
Number of pages6
JournalHypertension
Volume67
Issue number2
DOIs
StatePublished - Feb 1 2016

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Mineralocorticoid Receptors
Hypertension
Blood Pressure
Placebos
Aldosterone
Renin
Angiotensin II
Pure Autonomic Failure
Mineralocorticoid Receptor Antagonists
Nocturia
Multiple System Atrophy
Mineralocorticoids
Angiotensin Type 1 Receptor
Orthostatic Hypotension
Angiotensins
Double-Blind Method
Cross-Over Studies
Parkinson Disease
Weight Loss
eplerenone

All Science Journal Classification (ASJC) codes

  • Internal Medicine

Cite this

Arnold, A., Okamoto, L. E., Gamboa, A., Black, B. K., Raj, S. R., Elijovich, F., ... Biaggioni, I. (2016). Mineralocorticoid Receptor Activation Contributes to the Supine Hypertension of Autonomic Failure. Hypertension, 67(2), 424-429. https://doi.org/10.1161/HYPERTENSIONAHA.115.06617
Arnold, Amy ; Okamoto, Luis E. ; Gamboa, Alfredo ; Black, Bonnie K. ; Raj, Satish R. ; Elijovich, Fernando ; Robertson, David ; Shibao, Cyndya A. ; Biaggioni, Italo. / Mineralocorticoid Receptor Activation Contributes to the Supine Hypertension of Autonomic Failure. In: Hypertension. 2016 ; Vol. 67, No. 2. pp. 424-429.
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Arnold, A, Okamoto, LE, Gamboa, A, Black, BK, Raj, SR, Elijovich, F, Robertson, D, Shibao, CA & Biaggioni, I 2016, 'Mineralocorticoid Receptor Activation Contributes to the Supine Hypertension of Autonomic Failure', Hypertension, vol. 67, no. 2, pp. 424-429. https://doi.org/10.1161/HYPERTENSIONAHA.115.06617

Mineralocorticoid Receptor Activation Contributes to the Supine Hypertension of Autonomic Failure. / Arnold, Amy; Okamoto, Luis E.; Gamboa, Alfredo; Black, Bonnie K.; Raj, Satish R.; Elijovich, Fernando; Robertson, David; Shibao, Cyndya A.; Biaggioni, Italo.

In: Hypertension, Vol. 67, No. 2, 01.02.2016, p. 424-429.

Research output: Contribution to journalArticle

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T1 - Mineralocorticoid Receptor Activation Contributes to the Supine Hypertension of Autonomic Failure

AU - Arnold, Amy

AU - Okamoto, Luis E.

AU - Gamboa, Alfredo

AU - Black, Bonnie K.

AU - Raj, Satish R.

AU - Elijovich, Fernando

AU - Robertson, David

AU - Shibao, Cyndya A.

AU - Biaggioni, Italo

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N2 - Primary autonomic failure is characterized by disabling orthostatic hypotension, but at least half of these patients have paradoxical supine hypertension. Renin-angiotensin mechanisms were not initially thought to contribute to this hypertension because plasma renin activity is often undetectable in autonomic failure. Plasma aldosterone levels are normal, however, and we recently showed that plasma angiotensin II is elevated and acts at AT1 (angiotensin type 1) receptors to contribute to hypertension in these patients. Because aldosterone and angiotensin II can also bind mineralocorticoid receptors to elevate blood pressure, we hypothesized that mineralocorticoid receptor activation plays a role in the hypertension of autonomic failure. To test this hypothesis, we determined the acute effects of the mineralocorticoid receptor antagonist eplerenone (50 mg, oral) versus placebo on supine blood pressure in a randomized, double-blind, crossover study. Medications were given at 8:00 pm with blood pressure recorded every 2 hours for 12 hours. Ten primary autonomic failure patients with supine hypertension completed this study (7 pure autonomic failure, 2 multiple system atrophy, 1 parkinson's disease; 7 male; 70±2 years of age). Eplerenone maximally reduced supine systolic blood pressure by 32±6 mm Hg at 8 hours after administration (versus 8±10 mm Hg placebo, P=0.016), with no effect on nocturia (12-hour urine volume: 985±134 mL placebo versus 931±94 mL eplerenone, P=0.492; nocturnal weight loss:-1.19±0.15 kg placebo versus-1.18±0.15 kg eplerenone, P=0.766). These findings suggest that inappropriate mineralocorticoid receptor activation contributes to the hypertension of autonomic failure, likely independent of canonical mineralocorticoid effects, and provides rationale for use of eplerenone in these patients.

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