Effects remaining after withdrawal of long-term beta-receptor blockade Reduced heart rate and altered haemodynamic response to acute propranolol administration

Abstract

Central haemodynamics at rest and during exercise were studied in 14 male patients with moderate essential hypertension. Their circulatory state was studied before and immediately after intravenous administration of propranolol, 0.2 mg/kg body weight. In 8 of the patients an identical study was repeated after .2 months of oral propranolol therapy. This second study was performed when the oral therapy had been discontinued for >72 hours which exceeds the time necessary for complete metabolism and excretion of propranolol. Pulmonary oxygen uptake, arteriovenous oxygen difference, heart rate, and blood pressures in the subclavian artery, pulmonary artery, pulmonary wedge position, and right atrium were measured. Before oral treatment, propranolol injection caused significant reductions of oxygen uptake (5%), heart rate (13%), cardiac output ( 20%), and stroke volume ( - 10%), significant increments to systemic (35/3%) and pulmonary vascular resistance ( - 35%), and increased filling pressures for both ventricles during exercise. After long-term treatment and omission of the drug, the spontaneous heart rates at rest and during exercise were significantly lower than before treatment. Propranolol injection now still increased the ventricular filling pressures at exercise but caused no significant effects on oxygen uptake, heart rate, cardiac output, stroke volume, or systemic vascular resistance. It is concluded that long-term beta-receptor blockade leads to a physiological adaptation including a persistent relative bradycardia and almost complete abolition of the haemodynamic response to acute administration of a beta-receptor blocking agent. It is suggested that this adaptation, which resembles that of physical training, constitutes one mechanism whereby long-term beta-receptor blockade is able to reduce the arterial blood pressure.