Determination of the α-adrenergic blocking potency of drugs in humans is usually done by measuring the shift in the blood pressure versus logarithm of intravenous phenylephrine dose-response relationship. Change in blood pressure activates homeostatic reflexes that may change this relationship. This study examines the effect of autonomic (β1- and β2-adrenergic, parasympathetic, and α-adrenergic) blockade on the dose versus blood pressure response relationship to sequential doses of phenylephrine in humans. Phenylephrine dose responses were conducted under controlled conditions, during propranolol and atropine infusion, during prazosin-induced α1-adrenergic blockade, and during prazosin, propranolol, and atropine administration. Propranolol-atropine infusion decreased the threshold dose of phenylephrine required to increase mean blood pressure (p < 0.00001), increased the slope of the phenylephrine dose versus increase in mean blood pressure relationship (p = 0.019), and decreased the dose of phenylephrine required to increase mean blood pressure by 20 mm Hg (p < 0.00001). Determination of the α-adrenergic blocking potency of prazosin was not affected by autonomic blockade with propranolol and atropine (dose ratio 5.2 before and 5.0 after autonomic blockade; p = 0.465). We conclude that β1- and β2-adrenergic and muscarinic blockade increase sensitivity to phenylephrine by increasing the slope and decreasing the threshold dose of the phenylephrine dose-response curve, and that α-adrenergic-blocking potency of prazosin may be determined with or without blocking homeostatic blood pressure regulatory mechanisms in humans.
ASJC Scopus subject areas
- Pharmacology (medical)