Effects of spironolactone on sympathetic nerve activity and baroreflex function in patients with early hypertensive heart disease

Activation of the renin-angiotensin-aldosterone system (RAAS) could induce sympathoexcitation mediated by aldosterone in patients with primary hypertension and left ventricular hypertrophy. We hypothesised that aldosterone antagonism may suppress muscle sympathetic nerve activity (MSNA) and improve baroreflex function in subjects with beginning hypertensive heart disease. Eleven patients with mild to moderate primary hypertension and echocardiographic signs of early hypertensive heart disease received either oral spironolactone 25mg/day or placebo for four weeks in a double-blind, cross-over design. On the experimental day, resting biochemical parameters were determined, and MSNA was recorded by microneurography of the peroneal nerve at rest and during intravenous infusion of phenylephrine and nitroprusside. Furthermore, blood pressure (BP) and heart rate were measured non-invasively. Spironolactone increased basal levels of vasopressin, aldosterone and renin. Resting MSNA was higher during treatment with spironolactone compared with placebo (37.0±4.3 vs. 32.4±4.3 bursts/min, p=0.01), while BP and heart rate were not affected. Furthermore, spironolactone altered baroreflex control of MSNA (ΔMSNA / Δdiastolic BP) resulting in higher MSNA levels during nitroprusside infusion (b=-0.57 vs. b=0.05, t-value=2.80, 56 degrees of freedom, p<0.05). However, spironolactone did not affect baroreflex control of MSNA during phenylephrine infusion. Contrary to expectations, spironolactone activates MSNA at rest and during baroreceptor deactivation in patients with early hypertensive heart disease. This sympathoexcitatory effect may be mediated by central mineralocorticoid receptor blockade itself or alternatively, via the RAAS or the vasopressinergic system, which both seem activated during isolated aldosterone antagonism.