Differential effects of chlorthalidone Versus spironolactone on muscle sympathetic nerve activity in hypertensive patients

Dileep V. Menon, Debbie Arbique, Zhongyun Wang, Beverley Adams-Huet, Richard J. Auchus, Wanpen Vongpatanasin

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Context: Previous studies in rats indicated thatthiazide-type diuretics reduced blood pressure (BP) and triggered baroreflex-mediated increase in sympathetic nerve activity (SNA), whereas spironolactone exerted central sympathoinhibitory action in addition to diuretic effects. Objectives: The objectives were to determine effects of spironolactone and chlorthalidone on SNA and the role of SNA on diuretic-induced insulin resistance in human hypertension. Methods: We conducted a randomized crossover study in 23 untreated hypertensive patients in which we measured muscle SNA at baseline, after 1 and 3 months of chlorthalidone (12.5-25 mg/d), and after 1 and 3 months of spironolactone (50-75 mg/d). Ambulatory BP, baroreflex sensitivity, and indices of insulin resistance were also assessed at baseline and after 3 months of each drug treatment. Results: Chlorthalidone caused a similar reduction in ambulatory BP from baseline when compared with spironolactone (11 ± 2/4 ± 2 and 10 ± 2/4 ± 2 mm Hg, respectively). However, chlorthalidone increased SNA by 23% (P < 0.01) within 1 month of treatment, whereas spironolactone had no effect in the same subjects. SNA continued to be elevated after 3 months of chlorthalidone when compared with baseline and spironolactone. Baroreflex control of SNA was unaffected by either drug. Chlorthalidone increased indices of insulin resistance, which were significantly correlated with increases in SNA from baseline, whereas spironolactone had no effect in the same subjects. Conclusions: Our data suggest that chlorthalidone, the first-line drug therapy for hypertension, causes persistent activation of sympathetic nervous system and insulin resistance in hypertensive patients. These side effects, however, are avoided by spironolactone despite similar reduction in BP.

Original languageEnglish (US)
Pages (from-to)1361-1366
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume94
Issue number4
DOIs
StatePublished - Apr 2009

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Chlorthalidone
Spironolactone
Muscle
Muscles
Blood pressure
Insulin Resistance
Baroreflex
Diuretics
Insulin
Blood Pressure
Drug therapy
Hypertension
Sympathetic Nervous System
Neurology
Pharmaceutical Preparations
Cross-Over Studies
Rats
Chemical activation
Drug Therapy

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Differential effects of chlorthalidone Versus spironolactone on muscle sympathetic nerve activity in hypertensive patients. / Menon, Dileep V.; Arbique, Debbie; Wang, Zhongyun; Adams-Huet, Beverley; Auchus, Richard J.; Vongpatanasin, Wanpen.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 94, No. 4, 04.2009, p. 1361-1366.

Research output: Contribution to journalArticle

Menon, Dileep V. ; Arbique, Debbie ; Wang, Zhongyun ; Adams-Huet, Beverley ; Auchus, Richard J. ; Vongpatanasin, Wanpen. / Differential effects of chlorthalidone Versus spironolactone on muscle sympathetic nerve activity in hypertensive patients. In: Journal of Clinical Endocrinology and Metabolism. 2009 ; Vol. 94, No. 4. pp. 1361-1366.
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T1 - Differential effects of chlorthalidone Versus spironolactone on muscle sympathetic nerve activity in hypertensive patients

AU - Menon, Dileep V.

AU - Arbique, Debbie

AU - Wang, Zhongyun

AU - Adams-Huet, Beverley

AU - Auchus, Richard J.

AU - Vongpatanasin, Wanpen

PY - 2009/4

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N2 - Context: Previous studies in rats indicated thatthiazide-type diuretics reduced blood pressure (BP) and triggered baroreflex-mediated increase in sympathetic nerve activity (SNA), whereas spironolactone exerted central sympathoinhibitory action in addition to diuretic effects. Objectives: The objectives were to determine effects of spironolactone and chlorthalidone on SNA and the role of SNA on diuretic-induced insulin resistance in human hypertension. Methods: We conducted a randomized crossover study in 23 untreated hypertensive patients in which we measured muscle SNA at baseline, after 1 and 3 months of chlorthalidone (12.5-25 mg/d), and after 1 and 3 months of spironolactone (50-75 mg/d). Ambulatory BP, baroreflex sensitivity, and indices of insulin resistance were also assessed at baseline and after 3 months of each drug treatment. Results: Chlorthalidone caused a similar reduction in ambulatory BP from baseline when compared with spironolactone (11 ± 2/4 ± 2 and 10 ± 2/4 ± 2 mm Hg, respectively). However, chlorthalidone increased SNA by 23% (P < 0.01) within 1 month of treatment, whereas spironolactone had no effect in the same subjects. SNA continued to be elevated after 3 months of chlorthalidone when compared with baseline and spironolactone. Baroreflex control of SNA was unaffected by either drug. Chlorthalidone increased indices of insulin resistance, which were significantly correlated with increases in SNA from baseline, whereas spironolactone had no effect in the same subjects. Conclusions: Our data suggest that chlorthalidone, the first-line drug therapy for hypertension, causes persistent activation of sympathetic nervous system and insulin resistance in hypertensive patients. These side effects, however, are avoided by spironolactone despite similar reduction in BP.

AB - Context: Previous studies in rats indicated thatthiazide-type diuretics reduced blood pressure (BP) and triggered baroreflex-mediated increase in sympathetic nerve activity (SNA), whereas spironolactone exerted central sympathoinhibitory action in addition to diuretic effects. Objectives: The objectives were to determine effects of spironolactone and chlorthalidone on SNA and the role of SNA on diuretic-induced insulin resistance in human hypertension. Methods: We conducted a randomized crossover study in 23 untreated hypertensive patients in which we measured muscle SNA at baseline, after 1 and 3 months of chlorthalidone (12.5-25 mg/d), and after 1 and 3 months of spironolactone (50-75 mg/d). Ambulatory BP, baroreflex sensitivity, and indices of insulin resistance were also assessed at baseline and after 3 months of each drug treatment. Results: Chlorthalidone caused a similar reduction in ambulatory BP from baseline when compared with spironolactone (11 ± 2/4 ± 2 and 10 ± 2/4 ± 2 mm Hg, respectively). However, chlorthalidone increased SNA by 23% (P < 0.01) within 1 month of treatment, whereas spironolactone had no effect in the same subjects. SNA continued to be elevated after 3 months of chlorthalidone when compared with baseline and spironolactone. Baroreflex control of SNA was unaffected by either drug. Chlorthalidone increased indices of insulin resistance, which were significantly correlated with increases in SNA from baseline, whereas spironolactone had no effect in the same subjects. Conclusions: Our data suggest that chlorthalidone, the first-line drug therapy for hypertension, causes persistent activation of sympathetic nervous system and insulin resistance in hypertensive patients. These side effects, however, are avoided by spironolactone despite similar reduction in BP.

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