Positive chronotropic responses to cardiac alpha 1-adrenoreceptor activation in the pithed rat

Adrenaline (0.1-10 micrograms/kg), noradrenaline (0.1-10 micrograms/kg) and phenylephrine (1-100 micrograms/kg) acted on both cardiac alpha 1- and beta-adrenoreceptors to induce positive chronotropic responses in the pithed rat. When beta-adrenoreceptors were blocked by propranolol (1 mg/kg), the residual chronotropic responses were due to activation of alpha 1-adrenoreceptors since they were significantly reduced by prazosin (10-100 micrograms/kg). Methoxamine (10-300 micrograms/kg) acted solely on cardiac alpha 1-adrenoreceptors to induce positive chronotropic responses which were abolished by prazosin (10-100 micrograms/kg) alone, as has been demonstrated previously for amidephrine. The rank order of potency for eliciting the positive chronotropic response to alpha 1-adrenoreceptor activation was adrenaline greater than noradrenaline greater than phenylephrine greater than methoxamine. The positive chronotropic responses to adrenaline (3-10 micrograms/kg), noradrenaline (3-10 micrograms/kg) and phenylephrine (30-100 micrograms/kg) produced by activating alpha 1-adrenoreceptors had a slower time course than did the chronotropic responses produced by activation of beta-adrenoreceptors.