Effect of angiotensin II receptor blockade on autonomic nervous system function in patients with essential hypertension. Am J Physiol Heart Circ Physiol 290: H1706–H1712

It has long been proposed that the renin-angiotensin system exerts a stimulatory influence on the sympathetic nervous system, including the augmentation of central sympathetic outflow and presynaptic facilitation of norepinephrine release from sympathetic nerves. We tested this proposition in 19 patients with essential hypertension, evaluating whether the angiotensin receptor blockers, eprosartan and losartan, had identifiable antiadrenergic properties. This was done in a prospective, randomised, three-way placebo controlled study of cross-over design. Patients were randomised to eprosartan 600mg daily, losartan 50mg daily or placebo. The treatment period was four weeks, with two week wash-out periods. Multiunit firing rates in efferent sympathetic nerves distributed to skeletal muscle vasculature (MSNA), was measured using microneurography, testing whether angiotensin receptor blockers (ARBs) inhibit central sympathetic outflow. In parallel, isotope dilution methodology was used to measure whole-body norepinephrine spillover to plasma. Mean blood pressure on placebo was 151/98 mmHg, with both ARBs causing reductions of approximately 11 mmHg systolic and 6 mmHg diastolic pressure, placebo-corrected. Both MSNA, 35±12 bursts/min (mean ± SD) on placebo, an