The effect of intrinsic sympathomimetic activity on beta‐receptor responsiveness after beta‐adrenoceptor blockade withdrawal.

1 Heart rate (HR) and blood pressure (BP) changes supine, at 60 degrees tilt and in response to increasing exercise loads, and HR responses to Valsalva's manoeuvre and to isoprenaline bolus injections were studied in 19 healthy volunteers to assess the response to abrupt withdrawal of atenolol n = 6, propranolol n = 6 and pindolol n = 7. 2 The dosage of each drug administered double-blind was gradually increased over a period of 2 weeks and the dose to produce maximum inhibition of exercise-induced tachycardia was continued for one further week. 3 Plasma renin activity, plasma noradrenaline and serum free thyroid hormones were measured during control periods, maximum dosage and withdrawal periods. 4 An increased sensitivity to isoprenaline injections was seen on Day 5 after withdrawal in the atenolol treated group whereas the pindolol treated group showed decreasing hyposensitivity to isoprenaline for the 13 days of observation after withdrawal and propranolol showed an intermediate effect. 5 There was no overshoot in HR or BP measurements at rest or in response to tilting, Valsalva's manoeuvre or exercise with atenolol or propranolol and with pindolol the HR response to tilt only was significantly higher on the third day post-drug. 6 Plasma noradrenaline and serum free T3 were reduced on drug treatment and further reduced in the early withdrawal period but there were no consistent changes in plasma renin activity.