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Human Cardiac β 1 ‐ or β 2 ‐Adrenergic Receptor Stimulation and the Negative Chronotropic Effect of Low‐Dose Pirenzepine
Author(s) -
Jakubetz Jens,
Schmuck Saskia,
Wochatz Germar,
Ruhland Barbara,
Poller Ulrike,
Radke Joachim,
Brodde OttoErich
Publication year - 2000
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1067/mcp.2000.105989
Subject(s) - pirenzepine , muscarinic acetylcholine receptor , medicine , chronotropic , endocrinology , heart rate , terbutaline , atropine , metoprolol , stimulation , propranolol , receptor , blood pressure , asthma
Objectives The M 1 ‐muscarinic receptor antagonist pirenzepine in low doses (<1 mg intravenously) decreases heart rate. We investigated whether these effects of pirenzepine differ in volunteers with activated cardiac β 1 ‐adrenergic receptors versus activated cardiac β 2 ‐adrenergic receptors. Methods In 17 male volunteers (25 ± 1 years) we studied effects of pirenzepine infusion (0.5 mg intravenous bolus followed by continuous infusion of 0.15 μg/kg/min) on heart rate and heart rate–corrected duration of electromechanical systole (QS 2 c, as a measure of inotropism) that had been stimulated by activation of cardiac β 1 ‐adrenergic receptors (bicycle exercise in the supine position for 60 minutes at 25 W) or cardiac β 2 ‐adrenergic receptors (continuous intravenous infusion of 100 ng/kg/min terbutaline). Results Bicycle exercise and terbutaline infusion significantly increased heart rate and shortened QS 2 c. When pirenzepine was infused 20 minutes after the beginning of the exercise or terbutaline infusion, heart rate decreased in both settings by approximately the same extent (approximately −10 to −14 beats/min), although exercise and terbutaline infusion continued; however, QS 2 c was not affected. Pirenzepine (0.05 to 1 mg intravenous bolus)‐induced decrease in heart rate was abolished after 6 days of transdermal scopolamine treatment of volunteers. Conclusions Low‐dose pirenzepine decreased heart rate by muscarinic receptor stimulation, because this was blocked by scopolamine. Moreover, low‐dose pirenzepine did not differentiate between cardiac β 1 ‐ or β 2 ‐adrenergic receptor stimulation; however, low‐dose pirenzepine did not affect cardiac contractility as measured by QS 2 c. Low‐dose pirenzepine therefore exerted a unique pattern of action in the human heart: it decreased heart rate (basal and β 1 ‐ and/or β 2 ‐adrenergic receptor‐stimulated) without affecting contractility. Clinical Pharmacology & Therapeutics (2000) 67 , 549–557; doi: 10.1067/mcp.2000.105989