Effect of prolonged propranolol administration and withdrawal on perfusion of the myocardial capillary bed.

Abstract

The effect of chronic propranolol administration (2 mg.kg-1.d-1 for 14d) and withdrawal on microvascular perfusion was studied in rabbit myocardium. Fluorescein isothiocyanate-dextran was injected into four groups of anaesthetised open chest rabbits. Fluorescent microscopy was used to identify the perfused vessels and alkaline phosphatase stain was employed to locate the total microvasculature. Beta adrenoceptor density (Bmax), measured using 125I-iodopindolol, increased from 20.3(SD 6.3) fmol.mg-1 protein in control to 52.4(8.9) in chronically treated rabbits. The proportion of the capillary bed which was perfused, 61.4(4.3)% was significantly decreased by acute injection of propranolol to 51.1(5.1)%, but not affected by chronic administration, remaining at 57.0(4.0)%. The percentage of the capillary bed perfused increased significantly after cessation of chronic propranolol treatment to 69.1(6.5)%. Similar results were seen for myocardial arterioles. Thus, while diffusion distances are increased by acute adrenoceptor blockade, this effect is not seen in the chronic condition. Diffusion distance decreased significantly after withdrawal of chronic propranolol treatment. We conclude that the percentage of perfused capillaries is strongly influenced by the number of beta adrenoceptors or their effect.