Sympathetically mediated hypertension in autonomic failure

Background-Approximately 50% of patients with primary autonomic failure hav e supine hypertension. We investigated whether this supine hypertension cou ld be driven by residual sympathetic activity. Methods and Results-In patients with multiple system atrophy (MSA) or pure autonomic failure (PAF), we studied the effect of oral yohimbine on seated systolic blood pressure (SBP), the effect of ganglionic blockade (with trim ethaphan) on supine SEP and plasma catecholamine levels, and the effect of alpha(1)-adrenoreceptor blockade (phenotolamine) on supine SBP. The SBP res ponse to yohimbine was greater in patients with MSA than in those with PAF (area under the curve, 2248+/-543 versus 467+/-209 mm Hg . min; P=0.022). M SA patients with a higher supine SEP had a greater response than those with a lower supine SEP (3874+/-809 versus 785+/-189 mm Hg.min; P=0.0017); this relationship was not seen in PAF patients. MSA patients had a marked depre ssor response to low infusion rates of trimethaphan; the response in PAF pa tients was more variable. Plasma norepinephrine decreased in both groups, b ut heart rate did not change in either group. At 1 mg/min, trimethaphan dec reased supine SEP by 67+/-8 and 12+/-6 mm Hg in MSA and PAF patients, respe ctively (P<0.0001). Cardiac index and total peripheral resistance decreased in MSA patients by 33.4+/-5.8% and 40.7+9.5%, respectively (P=0.0015). Pat ients having a depressor response to trimethaphan also had a depressor resp onse to phentolamine. In MSA patients, the presser response to yohimbine an d the decrease in SBP with 1 mg/min trinlethaphan were correlated (r=0.98; P=0.001). Conclusions-Residual sympathetic activity drives supine hypertension in MSA . It contributes to, but does not completely explain, supine hypertension i n PAF.