Sympathetically mediated hypertension in autonomic failure

Area of Science:

• Autonomic Nervous System Physiology
• Cardiovascular Regulation
• Neurology

Background:

• Supine hypertension affects approximately 50% of patients with primary autonomic failure.
• The role of residual sympathetic activity in driving this supine hypertension is not fully understood.

Purpose of the Study:

• To investigate whether residual sympathetic activity is the cause of supine hypertension in patients with primary autonomic failure.
• To differentiate the mechanisms of supine hypertension in multiple system atrophy (MSA) and pure autonomic failure (PAF).

Main Methods:

• Studied the effects of yohimbine (alpha-2 antagonist), trimethaphan (ganglionic blockade), and phentolamine (alpha-1 blockade) on blood pressure in MSA and PAF patients.
• Measured systolic blood pressure (SBP), plasma catecholamine levels, cardiac index, and total peripheral resistance.

Main Results:

• Yohimbine's effect on SBP was significantly greater in MSA patients compared to PAF patients.
• Ganglionic blockade with trimethaphan markedly reduced supine SBP in MSA patients, but had a more variable effect in PAF patients.
• A strong correlation was observed between the pressor response to yohimbine and the depressor response to trimethaphan in MSA patients.

Conclusions:

• Residual sympathetic activity is the primary driver of supine hypertension in multiple system atrophy (MSA).
• Residual sympathetic activity contributes to, but does not entirely account for, supine hypertension in pure autonomic failure (PAF).