Cardiac alpha-adrenoceptors involving positive chronotropic responses

Phenylephrine, adrenaline, and noradrenaline have been shown to act on both alpha- and beta-adrenoceptors to produce an increase in heart rate in the pithed rat and rat isolated atria. Abolition of these responses requires blockade of both types of adrenoceptors. The rank order of alpha-adrenoceptor agonists to produce positive chronotropic responses was adrenaline greater than noradrenaline greater than phenylephrine greater than methoxamine. In the case of methoxamine, positive chronotropic responses were largely due to the activation of alpha 1-adrenoceptors. The positive chronotropic responses to activation of alpha 1-adrenoceptors developed more slowly than did the response to beta-adrenoceptor activation in the pithed rat. The fact that blockade of one receptor type enhanced the positive chronotropic responses to activation of the other receptor type suggests that there may be an interaction between the cardiac alpha 1- and beta-adrenoceptors mediating positive chronotropic responses. In the rat isolated atria, the calcium antagonists verapamil (10 nmol/L) and nifedipine (10 nmol/L) also inhibited the alpha 1-adrenoceptor-mediated positive chronotropic effect of phenylephrine to the same extent as prazosin (10 nmol/L). Prazosin was not a calcium antagonist, as shown by its failure to block the contracture of the depolarized rat isolated aortic strips. Neither verapamil nor nifedipine were alpha 1-adrenoceptor antagonists at these concentrations.