This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Menon, D. V. Articles by Vongpatanasin, W. Search for Related Content PubMed PubMed Citation Articles by Menon, D. V. Articles by Vongpatanasin, W. Related Collections Adrenal and Hypertension

Differential Effects of Chlorthalidone Versus Spironolactone on Muscle Sympathetic Nerve Activity in Hypertensive Patients

Departments of Internal Medicine (D.V.M., D.A., Z.W., R.J.A., W.V.) and Clinical Sciences (B.A.-H.) and the Donald W. Reynolds Cardiovascular Clinical Research Center (W.V.), University of Texas Southwestern Medical Center, Dallas, Texas 75390

Address all correspondence and requests for reprints to: Dr. Vongpatanasin, Hypertension Division, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, J4.134, Dallas, Texas 75390-8586. E-mail: wanpen.vongpatanasin{at}utsouthwestern.edu.

Context: Previous studies in rats indicated that thiazide-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.

This article has been cited by other articles:

				G. Jain, R. C. Campbell, and D. G. Warnock Mineralocorticoid Receptor Blockers and Chronic Kidney Disease Clin. J. Am. Soc. Nephrol., October 1, 2009; 4(10): 1685 - 1691. [Abstract] [Full Text] [PDF]