alpha 1-adrenoceptor activation can increase heart rate directly or decrease it indirectly through parasympathetic activation.

1 The chronotropic effects of alpha- and beta-adrenoceptor agonists were investigated in the pithed rat. 2 The beta-adrenoceptor agonist, isoprenaline, produced only a positive chronotropic response. alpha 1-Adrenoceptor agonists, phenylephrine and amidephrine, produced positive and negative chronotropic effects. Part of the response to phenylephrine was beta-mediated. 3 A positive chronotropic response to amidephrine and phenylephrine was mediated directly through cardiac alpha 1-adrenoceptors and had a different time course from beta-adrenoceptor-mediated responses. 4 A negative chronotropic response to alpha-agonists was potentiated by neostigmine and blocked by atropine, tetrodotoxin or hexamethonium as well as by alpha 1-adrenoceptor antagonists. This may indicate alpha 1-adrenoceptors on preganglionic parasympathetic nerves, stimulation of these receptors causing release of acetylcholine. 5 The alpha 2-adrenoceptor agonist, xylazine, produced a direct negative chronotropic effect on the heart, independent of alpha-adrenoceptors. No evidence was found for functional post-junctional alpha 2-adrenoceptors. At high doses xylazine stimulated cardiac alpha 1-adrenoceptors.