Reduction in sympathetic nervous activity as a mechanism for hypotensive effect of propranolol

Abstract

THE β-adrenoceptor antagonist propranolol is an effective antihypertensive drug in man¹ but it is not known how the fall in blood pressure is produced². There is a decrease in plasma renin activity³ and in cardiac output immediately on starting propranolol therapy but neither of these effects can explain fully the hypotensive action of the drug which is delayed in onset and associated with a reduction in peripheral vascular resistance⁴. It has been suggested that the fall in blood pressure after propranolol results from blockade of β-like adrenoceptors within the central nervous system⁵. Thus, intracerebroventricular injection of propranolol lowers blood pressure in conscious cats⁵ and rabbits⁶, an effect which is specific for the β-blocking (—) isomer of the drug⁷. The effective concentration of propranolol achieved in the hypothalamus by this route of administration is within the range predicted for hypertensive patients after chronic oral therapy⁸. We now present direct evidence that propranolol diminishes sympathetic nerve activity in the rabbit and that this central effect contributes to the hypotensive action of the drug.