Chronic renin inhibition lowers blood pressure and reduces upright muscle sympathetic nerve activity in hypertensive seniors

Yoshiyuki Okada, Sara S Jarvis, Stuart A. Best, Tiffany B. Bivens, Beverley Adams-Huet, Benjamin D. Levine, Qi Fu

Research output: Contribution to journalArticle

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Abstract

Cardiovascular risk remains high in patients with hypertension even with adequate blood pressure (BP) control. One possible mechanism may be sympathetic activation via the baroreflex. We tested the hypothesis that chronic inhibition of renin reduces BP without sympathetic activation, but diuresis augments sympathetic activity in elderly hypertensives. Fourteen patients with stage-I hypertension (66 ± 5 (SD) years) were treated with a direct renin inhibitor, aliskiren (n= 7), or a diuretic, hydrochlorothiazide (n= 7), for 6 months. Muscle sympathetic nerve activity (MSNA), BP, direct renin and aldosterone were measured during supine and a graded head-up tilt (HUT; 5 min 30° and 20 min 60°), before and after treatment. Sympathetic baroreflex sensitivity (BRS) was assessed. Both groups had similar BP reductions after treatment (all P < 0.01), while MSNA responses were different between hydrochlorothiazide and aliskiren (P= 0.006 pre/post × drug). Both supine and upright MSNA became greater after hydrochlorothiazide treatment (supine, 72 ± 18 post vs. 64 ± 15 bursts (100 beats)-1 pre; 60° HUT, 83 ± 10 vs. 78 ± 13 bursts (100 beats)-1; P= 0.002). After aliskiren treatment, supine MSNA remained unchanged (69 ± 13 vs. 64 ± 8 bursts (100 beats)-1), but upright MSNA was lower (74 ± 15 vs. 85 ± 10 bursts (100 beats)-1; P= 0.012 for pre/post × posture). Direct renin was greater after both treatments (both P < 0.05), while upright aldosterone was greater after hydrochlorothiazide only (P= 0.002). The change in upright MSNA by the treatment was correlated with the change of aldosterone (r= 0.74, P= 0.002). Upright sympathetic BRS remained unchanged after either treatment. Thus, chronic renin inhibition may reduce upright MSNA through suppressed renin activity, while diuresis may evoke sympathetic activation via the upregulated renin-angiotensin-aldosterone system, without changing intrinsic sympathetic baroreflex function in elderly hypertensive patients.

Original languageEnglish (US)
Pages (from-to)5913-5922
Number of pages10
JournalJournal of Physiology
Volume591
Issue number23
DOIs
StatePublished - Dec 2013
Externally publishedYes

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Renin
Hydrochlorothiazide
Blood Pressure
Baroreflex
Muscles
Aldosterone
Diuresis
Therapeutics
Hypertension
Renin-Angiotensin System
Posture
Diuretics
Head
Pharmaceutical Preparations
aliskiren

ASJC Scopus subject areas

  • Physiology

Cite this

Chronic renin inhibition lowers blood pressure and reduces upright muscle sympathetic nerve activity in hypertensive seniors. / Okada, Yoshiyuki; Jarvis, Sara S; Best, Stuart A.; Bivens, Tiffany B.; Adams-Huet, Beverley; Levine, Benjamin D.; Fu, Qi.

In: Journal of Physiology, Vol. 591, No. 23, 12.2013, p. 5913-5922.

Research output: Contribution to journalArticle

Okada, Yoshiyuki ; Jarvis, Sara S ; Best, Stuart A. ; Bivens, Tiffany B. ; Adams-Huet, Beverley ; Levine, Benjamin D. ; Fu, Qi. / Chronic renin inhibition lowers blood pressure and reduces upright muscle sympathetic nerve activity in hypertensive seniors. In: Journal of Physiology. 2013 ; Vol. 591, No. 23. pp. 5913-5922.
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