TY - JOUR
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
N1 - Funding Information:
This work was supported by grants to W.V. from the National Institutes of Health (RO1HL-078782), the O'Brien Kidney Center, and the Donald W. Reynolds Foundation; to R.J.A. from the Clinical Scientist Award in Translational Research 1005954 from the Burroughs Wellcome Fund; to B.A.-H. from the Clinical and Translational Sciences Award (UL1RR-024982); and to D.V.M. from the American Society of Hypertension (Texas Chapter).
Funding Information:
Disclosure Summary: W.V. is supported by research grant from the National Institutes of Health (RO1HL-078782). Other authors have nothing to declare.
PY - 2009/4
Y1 - 2009/4
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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U2 - 10.1210/jc.2008-2660
DO - 10.1210/jc.2008-2660
M3 - Article
C2 - 19158191
AN - SCOPUS:65249137181
SN - 0021-972X
VL - 94
SP - 1361
EP - 1366
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 4
ER -