α ₁‐ADRENOCEPTOR ACTIVATION CAN INCREASE HEART RATE DIRECTLY OR DECREASE IT INDIRECTLY THROUGH PARASYMPATHETIC ACTIVATION

The chronotropic effects of α‐ and β‐adrenoceptor agonists were investigated in the pithed rat. The β‐adrenoceptor agonist, isoprenaline, produced only a positive chronotropic response. α₁‐Adrenoceptor agonists, phenylephrine and amidephrine, produced positive and negative chronotropic effects. Part of the response to phenylephrine was β‐mediated. A positive chronotropic response to amidephrine and phenylephrine was mediated directly through cardiac α₁‐adrenoceptors and had a different time course from β‐adrenoceptor‐mediated responses. A negative chronotropic response to α‐agonists was potentiated by neostigmine and blocked by atropine, tetrodotoxin or hexamethonium as well as by α₁‐adrenoceptor antagonists. This may indicate α₁‐adrenoceptors on preganglionic parasympathetic nerves, stimulation of these receptors causing release of acetylcholine. The α₂‐adrenoceptor agonist, xylazine, produced a direct negative chronotropic effect on the heart, independent of α‐adrenoceptors. No evidence was found for functional post‐junctional α₂‐adrenoceptors. At high doses xylazine stimulated cardiac α₁‐adrenoceptors. 1982 British Pharmacological Society