Methods for measuring vascular and nonvascular alpha-receptor sensitivity in humans

Area of Science:

• Cardiovascular Physiology
• Pharmacology
• Hypertension Research

Background:

• Increased alpha-adrenergic reactivity is implicated in essential hypertension pathophysiology.
• Accurate in vivo assessment of human alpha-receptor sensitivity is needed.

Purpose of the Study:

• To assess alpha-receptor sensitivity using pupillometry and intraarterial infusions.
• To create an in vivo environment with decreased sympathetic drive and increased alpha-receptor number.
• To determine if increased alpha-receptor sensitivity occurs under these conditions.

Main Methods:

• Five patients with minimally elevated blood pressure on diuretic monotherapy were studied.
• Physiological and biochemical variables were assessed on diuretic alone and with guanadrel.
• Pupillometry and forearm intraarterial infusions were used to measure alpha-receptor responses.

Main Results:

• Guanadrel plus diuretic lowered blood pressure and heart rate compared to diuretic alone.
• Plasma norepinephrine levels decreased by 40% (p=0.03).
• Platelet alpha-2 receptors increased by 40% (p=0.07), but pupillary and forearm responses to agonists were not augmented.

Conclusions:

• The study failed to demonstrate increased physiological responsiveness despite reduced sympathetic drive and increased alpha-2 receptor numbers.
• Multiple explanations for this lack of enhanced responsiveness require further investigation.