Sympathetically mediated hypertension in autonomic failure

• Published in: Circulation (New York, N.Y.) Vol. 101; no. 23; pp. 2710 - 2715
• Main Authors: Shannon, J. R., Jordan, J., Diedrich, A., Pohar, B., Black, B. K., Robertson, D., Biaggioni, I., Roberton, D.
• Format: Journal Article
• Language: English
• Published: Legacy CDMS Lippincott Williams & Wilkins 13-06-2000; American Heart Association, Inc
• Subjects: Adrenergic alpha-Antagonists - administration & dosage; Aged; Antihypertensive Agents - administration & dosage; Autonomic Nervous System Diseases - complications; Autonomic Nervous System Diseases - physiopathology; Biological and medical sciences; Blood Pressure - drug effects; Cardiac Output - drug effects; Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction; Female; Ganglionic Blockers - administration & dosage; Heart - innervation; Heart - physiopathology; Heart Failure - complications; Heart Failure - physiopathology; Heart Rate - drug effects; Humans; Hypertension - complications; Hypertension - drug therapy; Hypertension - physiopathology; Life Sciences (General); Male; Medical sciences; Multiple System Atrophy - complications; Multiple System Atrophy - physiopathology; Nervous system (semeiology, syndromes); Neurology; Norepinephrine - blood; Phentolamine - administration & dosage; Reflex - physiology; Space life sciences; Sympathetic Nervous System - physiopathology; Trimethaphan - administration & dosage; Vascular Resistance - drug effects; Yohimbine - administration & dosage; Clinical Trial; Non-Nasa Center; Nasa Discipline Regulatory Physiology; Human; Hypertension; Pharmacologic test; Nervous system diseases; Pathophysiology; Yohimbine; α1-Adrenergic receptor; Supination; Cardiovascular disease; Exploration; Catecholamine; Trimetaphan camsilate; Ganglioplegic; Alpha blocking agent; Diseases of the autonomic nervous system; Multiple system atrophy; Complication; Blood pressure; Antagonist; Phentolamine; Comparative study; NASA Discipline Regulatory Physiology; Non-NASA Center
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.cir.101.23.2710

BACKGROUND: Approximately 50% of patients with primary autonomic failure have supine hypertension. We investigated whether this supine hypertension could 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 trimethaphan) on supine SBP and plasma catecholamine levels, and the effect of alpha(1)-adrenoreceptor blockade (phentolamine) on supine SBP. The SBP response 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). MSA patients with a higher supine SBP had a greater response than those with a lower supine SBP (3874+/-809 versus 785+/-189 mm Hg. min; P=0. 0017); this relationship was not seen in PAF patients. MSA patients had a marked depressor response to low infusion rates of trimethaphan; the response in PAF patients was more variable. Plasma norepinephrine decreased in both groups, but heart rate did not change in either group. At 1 mg/min, trimethaphan decreased supine SBP by 67+/-8 and 12+/-6 mm Hg in MSA and PAF patients, respectively (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). Patients having a depressor response to trimethaphan also had a depressor response to phentolamine. In MSA patients, the pressor response to yohimbine and the decrease in SBP with 1 mg/min trimethaphan 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 in PAF.