Competitive blockade of alpha-adrenergic receptors in rat heart by prazosin

Phenylephrine (PE) in presence of propranolol evokes an alpha-adrenergic inotropic response in rat heart. The time course of this response is characterized by a transient decrease in maximal developed tension (Tmax) to subcontrol levels (negative phase of the inotropic response) followed by an increase which reaches maximum after 4-5 min. (positive phase of the inotropic response). Prazosin (PRZ), a selective alpha 1-receptor blocker, inhibited preferentially the positive phase of the inotropic response and displaced the dose-response curve of PE to the right in nanomolar concentrations, indicating a competitive mechanism of inhibition. Phentolamine, a non-selective alpha-blocker, blocked both the negative and the positive phase of the inotropic response to about the same degree. PRZ appears to be a competitive alpha-adrenergic antagonist with high affinity in rat heart. Two populations of alpha-adrenergic receptors may be present: one stimulatory (alpha 1) and one inhibitory.