N(N)-nicotinic blockade as an acute human model of autonomic failure

Abstract

Pure autonomic failure has been conceptualized as deficient sympathetic and parasympathetic innervation. Several recent observations in chronic autonomic failure, however, cannot be explained simply by loss of autonomic innervation, at least according to our current understanding. To simulate acute autonomic failure, we blocked N(N)-nicotinic receptors with intravenous trimethaphan (6±0.4 mg/min) in 7 healthy subjects (4 men, 3 women, aged 32±3 years, 68±4 kg, 171±5 cm). N(N)-Nicotinic receptor blockade resulted in near-complete interruption of sympathetic and parasympathetic efferents as indicated by a battery of autonomic function tests. With trimethaphan, small postural changes from the horizontal were associated with significant blood pressure changes without compensatory changes in heart rate. Gastrointestinal motility, pupillary function, saliva production, and tearing were profoundly suppressed with trimethaphan. Plasma norepinephrine level decreased from 1.1±0.12 nmol/L (180±20 pg/mL) at baseline to 0.23±0.05 nmol/L (39±8 pg/mL) with trimethaphan (P