Cardiac hyper- and hyporesponsiveness after pindolol withdrawal

Area of Science:

• Cardiology
• Pharmacology
• Adrenergic Receptor Physiology

Background:

• Abrupt beta-blocker withdrawal can cause adrenergic hypersensitivity due to increased cardiac beta-receptor responsiveness.
• Pindolol's partial agonist activity was hypothesized to mitigate these withdrawal effects.

Purpose of the Study:

• To investigate the effects of abrupt pindolol withdrawal on cardiac beta-receptor responsiveness in hypertensive patients.
• To determine if pindolol's partial agonist activity prevents or reduces withdrawal-induced adrenergic hypersensitivity.

Main Methods:

• 10 hypertensive patients received pindolol (10 mg b.i.d.) for at least 4 weeks.
• Pindolol was then abruptly replaced with placebo for 20 days.
• Cardiac chronotropic responsiveness to isoproterenol, resting/exercise heart rate, and blood pressure were monitored.

Main Results:

• Cardiac chronotropic responsiveness to isoproterenol decreased during pindolol treatment and returned to normal over 10-20 days post-withdrawal.
• Resting and exercise heart rates showed a transient rebound increase in responsiveness between days 2-6 after pindolol withdrawal (P < 0.05).
• Blood pressure gradually increased to stable levels without rebound; plasma catecholamines and thyroid hormones remained unchanged.

Conclusions:

• Abrupt pindolol withdrawal induces transient cardiac hyperresponsiveness in heart rate but persistent hyporesponsiveness to isoproterenol.
• These findings indicate differential effects of pindolol on subsets of cardiac beta-adrenergic chronotropic receptors.
• Pindolol's partial agonist activity may modulate withdrawal-induced receptor hypersensitivity differently across various cardiac beta-adrenergic receptor functions.