Histamine can produce inotropic and chronotropic responses in both guinea pig and
rabbit heart. In the guinea pig the responses are mediated primarily through stimulation
of H2 receptors with H1 receptors being found mainly in left atria. In the rabbit
H1 receptors predominate; H2 receptors are found only in right atria and are partially
responsible for the chronotropic effect. H2 receptors are always associated with cyclic
AMP, whereas H1 receptors are not. H2-histamine receptors and beta-adrenergic receptors
have a number of properties in common. Stimulation of either receptor results in positive
inotropic and chronotropic effects and increases in cyclic AMP and phosphorylase a.
H2 and beta-adrenergic agonists will also both restore the action potential in K+-depolarized
cardiac muscle. H1 and alpha-agonists, on the other hand, will also produce an inotropic
effect. The effect is not dependent on cyclic AMP and can only be demonstrated under
certain conditions. Neither agonist will restore the action potential in depolarized
cardiac tissue. It is concluded that, although H2 and beta-agonists and H1 and alpha-agonists
may have a common mechanism of action, the two groups of drugs (H2, beta versus H1,
alpha) differ from each other with regard to mechanism.