WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: A sympatho-inhibitory effect of ACE-inhibitors and AT(1) receptor antagonists has been widely demonstrated in animal models, but in humans this effect tends only to be present during chronic treatment in conditions with pre-existing high levels of sympathetic activity. Sodium restriction increases renal sympathetic nerve activity and the activity of the renin-angiotensin system and may be a favourable condition to demonstrate sympatho-inhibition as a short-term effect of the AT(1) receptor antagonist eprosartan in healthy humans. WHAT THIS STUDY ADDS: Results from our study indicate that during sodium restrictioneprosartan has a small inhibitory effect on nonbaroreflex mediated activation of the sympathetic nervous system. During arterial baroreflex mediated activation of the sympathetic nervous system this effect is, however, completely overruled by an increased sensitivity of the arterial baroreflex. AIMS To test the hypothesis that eprosartan inhibits both nonbaroreflex and arterial baroreflex mediated activation of the sympathetic nervous system, assessed by renal tubular function, systemic haemodynamics and vasoactive hormones, in sodium restricted healthy humans. METHODS: The effect of eprosartan on urinary sodium, lithium and water excretion, heart rate (HR), blood pressure and vasoactive hormones was measured before, during and after a cold pressor test (CPT) and sodium nitroprusside (SNP) infusion in a randomized, placebo controlled, double-blind, crossover study in 17 healthy subjects. Glomerular filtration rate and renal tubular function were determined by a continuous infusion clearance technique and vasoactive hormones by radioimmunoassays. RESULTS:Eprosartan attenuated the impact of the CPT on HR (mean difference from placebo (95% confidence interval) (3.9 (0.7, 7.0) min(-1)) and mean arterial pressure (MAP) (4.7 (0.3, 9.2) mmHg), but no effect of eprosartan was observed on the impact of the CPT on renal tubular function. During a SNP induced reduction in MAP of 10 mmHg eprosartan decreased fractional excretions of sodium (0.46 (0.14, 0.76)%) and lithium (5.1 (2.5, 7.6)%) and tended to increase HR (4.1 (-0.26, 8.4) min(-1)) and plasma concentrations of norepinephrine (33.8 (-5.8, 72.1) pg ml(-1)). CONCLUSIONS; These findings suggest that during mild sodium restrictioneprosartan has a small inhibitory effect on nonbaroreflex mediated activation of the sympathetic nervous system. During arterial baroreflex mediated activation of the sympathetic nervous system this effect is, however, completely overruled by an increased sensitivity of the arterial baroreflex.
RCT Entities:
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: A sympatho-inhibitory effect of ACE-inhibitors and AT(1) receptor antagonists has been widely demonstrated in animal models, but in humans this effect tends only to be present during chronic treatment in conditions with pre-existing high levels of sympathetic activity. Sodium restriction increases renal sympathetic nerve activity and the activity of the renin-angiotensin system and may be a favourable condition to demonstrate sympatho-inhibition as a short-term effect of the AT(1) receptor antagonist eprosartan in healthy humans. WHAT THIS STUDY ADDS: Results from our study indicate that during sodium restriction eprosartan has a small inhibitory effect on nonbaroreflex mediated activation of the sympathetic nervous system. During arterial baroreflex mediated activation of the sympathetic nervous system this effect is, however, completely overruled by an increased sensitivity of the arterial baroreflex. AIMS To test the hypothesis that eprosartan inhibits both nonbaroreflex and arterial baroreflex mediated activation of the sympathetic nervous system, assessed by renal tubular function, systemic haemodynamics and vasoactive hormones, in sodium restricted healthy humans. METHODS: The effect of eprosartan on urinary sodium, lithium and water excretion, heart rate (HR), blood pressure and vasoactive hormones was measured before, during and after a cold pressor test (CPT) and sodium nitroprusside (SNP) infusion in a randomized, placebo controlled, double-blind, crossover study in 17 healthy subjects. Glomerular filtration rate and renal tubular function were determined by a continuous infusion clearance technique and vasoactive hormones by radioimmunoassays. RESULTS:Eprosartan attenuated the impact of the CPT on HR (mean difference from placebo (95% confidence interval) (3.9 (0.7, 7.0) min(-1)) and mean arterial pressure (MAP) (4.7 (0.3, 9.2) mmHg), but no effect of eprosartan was observed on the impact of the CPT on renal tubular function. During a SNP induced reduction in MAP of 10 mmHg eprosartan decreased fractional excretions of sodium (0.46 (0.14, 0.76)%) and lithium (5.1 (2.5, 7.6)%) and tended to increase HR (4.1 (-0.26, 8.4) min(-1)) and plasma concentrations of norepinephrine (33.8 (-5.8, 72.1) pg ml(-1)). CONCLUSIONS; These findings suggest that during mild sodium restriction eprosartan has a small inhibitory effect on nonbaroreflex mediated activation of the sympathetic nervous system. During arterial baroreflex mediated activation of the sympathetic nervous system this effect is, however, completely overruled by an increased sensitivity of the arterial baroreflex.