Pharmacological Characterization of Adrenergic Alpha and Beta Receptors Mediating the Vasomotor Responses of Cerebral Arteries Ir Vitro

Abstract

The adrenergic receptors in the isolated feline middle cerebral artery were characterized pharmacologically using a sensitive system for recording circular contractions in vitro. Epinephrine. norepinephrine, isoproterenol. and phenylephrine contracted the vessel in the mentioned order of potency. Together with the inhibitory patterns obtained with graded doses of piperoxan (reversible competitive inhibition) and dibenamine or phenoxybenzamine (irreversible competitive inhibition), these results showed that the contraction was mediated by alpha receptors. With piperoxan and norepinephrine, the mean value for pA₂ was 7.06 and for K _H1.24 x 10^-7M. The mean value for K _A calculated for norepinephrine before and after partial irreversible blockade of the alpha receptors with phenoxybenzamine was 1.73 x 10^-6M. The norepinephrine response was not directly proportional to the amount of receptors occupied; ED₅₀ was reached when only about 11% of the receptors were occupied and the E_Am response was obtained when 75% of the receptors were occupied. Dilation was achieved only after an active tonic contraction had been induced (with 5-hydroxytryptamine) in the vessels, and the order of potency was isoproterenol > norepinephrine - epinephrine > terbutaline. Inhibition with INPEA and propranolol was competitive, as confirmed by Arunlakshana-Schild plots, showing that the dilatory response was a beta-receptor effect. The values for pA₂ (8.78 and 9.17) and K_H (2.31 x 10^-9M and 1.77 x 10^-9M) for propranolol were indistinguishable in tests with terbutaline and isoproterenol, respectively. Comparison of the relative potencies of norepinephrine and epinephrine as well as isoproterenol and terbutaline suggested that the receptors were of the beta₁ type.