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 pA, was 7.06 and for K H 1.24 > 10 7 M. 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"M. The norepinephrine response was not directly proportional to the amount of receptors occupied; ED 60 was reached when only about 11*7 of the receptors were occupied and the E Am response was obtained when 75 r 7 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 pA, (8.78 and 9.17) and K B (2.31 x 10~"M and 1.77 x 10~*M) 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 beta, type.

α-Adrenoreceptors and Muscarine Receptors in Human Pial Arteries and Micro Vessels: A Receptor Binding Study

“…In vitro application of catechol amines to pial vessels generally produces contrac tion (Kuschinsky and Wahl, 1975;Edvinsson et ai., 1976). Some authors have found biphasic dose-re sponse curves (Duckles and Bevan, 1976) to adren ergic agonists, and the low potency of norepineph rine and phenylephrine has led some investigators to suggest that a-receptors are different from those found in peripheral arteries (Edvinsson and Owman, 1974). Responses to intravascular cate cholamines have been less well studied in the brain, but studies with peripheral vessels have suggested the presence of endothelial a2-adrenoreceptors (Langer et ai., 1980;McGrath, 1982) and that these mediate relaxation (Cocks and Angus, 1983).…”

Effects of Bilirubin on Cerebral Arterial Tone in vitro

“…Consistent with previous findings in several spe cies (Duckles and Bevan, 1976;Lee et al, 1981), the NE contractile dose-response curves in cerebral arteries of the dog and cat were composed of two phases: an initial phase of smaller contractions in duced by NE in concentrations from 10 -6 to 3 X 10-4 M, followed by a second phase of sharply el evated contractile responses induced by higher con centrations ofNE 00-3 -3 x 10-3 M) ( sponses may be mediated by non-u-adrenergic receptors (Edvinsson and Owman, 1974;Bevan, 1981), the effect of bilirubin on the initial phase of NE dose-response curves was examined. In the presence of bilirubin (3 x 10-5 M), NE-induced contractions were usually similar to or smaller than the contractions induced before addition of bilirubin (Fig.…”

Characterization of beta adrenergic receptors in human cerebral arteries and alteration of the receptors after subarachnoid hemorrhage.

“…When the contraction is blocked by alpha adrenergic antagonists, isoproterenol induces relaxation, in a dose dependent manner in human, 1 -4 cat, 3 and dog 4 cerebral arteries. This relaxation was blocked by propranolol.…”