Abstract
β‐Adrenoceptor antagonists are used to treat a variety of cardiovascular disorders, and discontinuation is associated with severe side effects including palpitations and ventricular dysrhythmias. The objective of this study was to determine if changes in cardiac innervation density might contribute to these adverse effects. Adult rats received saline, the non‐selective β‐blocker propranolol, the selective β1‐blocker metoprolol, or the α‐blocker phentolamine for 7 days by minipump infusion. Ventricular sympathetic innervation increased 48% after propranolol and 44% after metoprolol treatment but was unchanged after phentolamine relative to saline controls. It seems unlikely that sympathetic sprouting is due to altered NGF release as neither α or β receptor agonists influenced NGF release in cultured cardiomyocytes. Propranolol or metoprolol increased neurite outgrowth by 17% and 29% respectively in cultured neonatal superior cervical ganglion neurons, suggesting that β‐blockers exert a direct effect on sympathetic axon outgrowth. The presence of β1 receptors in cultured neurons was confirmed by RT‐PCR. These results indicate that the blockade of β1 adrenergic receptors in vivo or in vitro leads to sympathetic axon sprouting, which may contribute to increased sympathetic tone observed in individuals undergoing withdrawal from β‐adrenergic receptor therapy. Supported by HL079652.
Published Version
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