Abstract 1415: Differential Effects of Chlorthalidone vs Spironolactone on Sympathetic Nerve Activity in Hypertensive Patients
Previous animal studies suggested that thiazide-type diuretics triggered reflex sympathetic activation, whereas mineralocorticoid receptor (MR) antagonists exerted central sympathoin-hibitory action in addition to diuretic effects. However, effect of MR antagonists on sympathetic nerve activity (SNA) has not been compared to thiazide-type diuretics in humans. Accordingly, we measured muscle SNA (microelectrodes inserted into peroneal nerve fascicles), 24-hour ambulatory blood pressure (ABP), and baroreflex control of SNA (modified Oxford technique) in 10 untreated hypertensive patients at baseline, after 3 months of chlorthalidone (12.5–25 mg/day), and after 3 months of spironolactone (50–75 mg/day), using randomized crossover design. ABP reduced to a similar extent with both diuretics compared with baseline (from 140±2.8/84±2.1 to 131±3.9/80±3.9 mmHg during chlorthalidone vs 130±2.8/79±2.6 mmHg during spironolactone). In contrast, SNA increased significantly with chlorthalidone (from 39±3 to 45±4 bursts/min, p < 0.05 vs baseline and < 0.01 vs spironolactone), while it was unaffected by spironolactone in the same subjects (38±3 bursts/min). Baroreflex gain was unaffected by treatment with either drug (from baseline −13.2±2.1 to −9.8±0.8 total activity/beat/mmHg during chlorthalidone vs −10.5±1.4 total activity/beat/mmHg during spironolactone, p < 0.05), indicating that failure of SNA to increase during spironolactone was not due to impaired baroreflex function. In conclusion, our data suggest that thiazide-type diuretics, the first-line drug therapy for hypertension, cause persistent activation of sympathetic nervous system in hypertensive patients. This side effect is avoided by MR antagonists, at the doses equally effective in reducing BP. Because sympathetic overactivity contributes to poor prognosis in patients with cardiovascular diseases, MR antagonists may constitute a safer alternative to thiazide-type diuretics for treatment of hypertension without compromising antihypertensive efficacy.