Mechanism of action of phenylephrine on isolated guinea-pig atria rate.

1. Phenylephrine has a positive chronotropic effect on the right isolated guinea-pig atria and this effect is not modified by alpha-adrenergic blocker (phentolamine) but it is drastically inhibited by beta-adrenergic antagonists (practolol or propranolol). 2. The effect is substantially reduced by treatment with cocaine or pretreatment with reserpine. 3. Cocaine plus reserpine shift the dose-response curve for phenylephrine to the left. 4. It is concluded that positive chronotropic effect of phenylephrine has two components: direct action on beta-adrenergic receptors and an indirect action due to norepinephrine release.