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Haemodynamic, metabolic, and lymphocyte beta 2-adrenoceptor changes following chronic beta-adrenoceptor antagonism
Abstract:
We have examined the effects of 7 days treatment with beta adrenoceptor antagonists in 8 healthy volunteers in a placebo controlled, crossover study. We investigated three beta-adrenoceptor antagonists (atenolol, oxprenolol, and propranolol), which have differing profiles of selectivity and partial agonist properties (intrinsic sympathomimetic activity, ISA). We studied adrenaline-induced hypokalaemia, the vasodilator response to an infusion of adrenaline (0.06 micrograms X kg-1 X min-1 for 90 min), and lymphocyte beta 2-adrenoceptor number, determined by (-) [125I]-iodocyanopindolol binding, and measured these variables both before and after 7 days of treatment. The beta 2-mediated depressor response to adrenaline infusion was abolished by propranolol and oxprenolol but persisted after atenolol. In contrast, the hypokalaemia induced by adrenaline was abolished by all three beta-blockers. Lymphocyte beta 2-adrenoceptor number increased significantly following propranolol treatment, but not after oxprenolol for atenolol. We conclude that up-regulation of lymphocyte beta 2-adrenoceptors is dependent on beta 2-receptor blockade and is modified by ISA. The reversal of the hypokalaemic response by atenolol suggests that beta 1 receptors may contribute to the former effect. Alternatively, since different populations of beta 2-adrenoceptors differ in their susceptibility to antagonists there may also be differences in agonist coupling to beta 2-responses between tissues.
Insights
Beta-blockers like atenolol, oxprenolol, and propranolol affect adrenaline responses. Propranolol and oxprenolol blocked adrenaline
Area of Science:
- Pharmacology
- Cardiovascular Physiology
- Adrenergic Receptor Research
Background:
- Beta-adrenoceptor antagonists are widely used for cardiovascular conditions.
- These drugs have varying selectivity and intrinsic sympathomimetic activity (ISA).
- Understanding their effects on adrenaline responses is crucial for clinical application.
Purpose of the Study:
- To investigate the effects of three beta-adrenoceptor antagonists (atenolol, oxprenolol, propranolol) on adrenaline-induced hypokalaemia and vasodilation.
- To examine the impact of these antagonists on lymphocyte beta 2-adrenoceptor number.
- To determine the role of receptor selectivity and ISA in mediating these effects.
Main Methods:
- A placebo-controlled, crossover study involving 8 healthy volunteers.
- Treatment with atenolol, oxprenolol, or propranolol for 7 days.
- Measurement of adrenaline-induced hypokalaemia, vasodilator response to adrenaline infusion, and lymphocyte beta 2-adrenoceptor number using (-) [125I]-iodocyanopindolol binding.
Main Results:
- Propranolol and oxprenolol abolished the beta 2-mediated depressor response to adrenaline, while atenolol did not.
- All three beta-blockers abolished adrenaline-induced hypokalaemia.
- Lymphocyte beta 2-adrenoceptor number increased significantly after propranolol but not after oxprenolol or atenolol.
Conclusions:
- Upregulation of lymphocyte beta 2-adrenoceptors depends on beta 2-receptor blockade and is influenced by ISA.
- The beta 1 receptor may contribute to the hypokalaemic response, or differential beta 2-adrenoceptor populations exist.
- Tissue-specific differences in beta 2-adrenoceptor coupling to responses may occur.