Characterization of norepinephrine-induced contractile response in isolated rabbit basilar artery.

It is well known that a-adrenoceptors have been classified into the a1-type in postsynaptic sites and the a2-type in presynaptic sites (1). Prazosin and yohimbine are selective an tagonists of a1 and a2-adrenoceptors, re spectively (2). Norepinephrine (NE) exerts a non-selective agonistic action at each type of a-adrenoceptors (3, 4). Recent reports present evidence that postsynaptic a2 as well as a,-adrenoceptors mediate vasocon strictor response (5, 6). It has been demon strated that the dose-response curve for NE shows a biphasic shape in isolated rabbit basilar artery (7-9). However, the mechanism by which the dose-response curve for NE shows the biphasic shape is not yet clear. Therefore, we studied the mechanism by which the dose-response curve for N E shows the biphasic shape, with special reference to the difference in extracellular calcium de pendence of contraction between the two phases of the dose-response curve for NE. A helically cut strip of basilar artery (about 20 mm in length) isolated from male albino rabbits weighing 2.0 to 3.0 kg was sus pended in a 20 ml organ bath filled with glucose, 6.0 mM) being main tained at 32±0.5°C and gassed with a mixture of 95% 02 and 5% C02. Tension development was measured isometrically using a force displacement transducer (San-Ei, Type 45196). Resting tension was adjusted to 0.25 g. After the basilar artery preparation was allowed to equilibrate for at least 1 hr, cumulative dose-response curves for NE were obtained. Antagonists or smooth muscle relaxants were added 5 min before the addition of NE. Exchange of normal buffer solution for lower calcium solutions (Ca21; 0.25 mM, 0.1 mM) was performed 15 min before the addition of NE. Drugs used in this study were papaverine hydrochloride (Tokyo Kasei), D 600 (methoxyverapamil, Knoll), 1-norepinephrine bitartrate (Wako Junyaku), prazosin hydrochloride (Pfizer) and yohimbine hydrochloride (Wako Junyaku). All the drugs were used as solutions in distilled water. In the isolated rabbit basilar artery, the dose-response curve for N E showed a biphasic shape which corresponded to the phase for lower NE concentrations and that for higher NE concentrations. In this paper, a part of the dose-response curve obtained by NE in the doses ranging from 10-8 M to 10-5 M was termed the "lower N E dose component", and the other obtained by NE in the doses ranging from 10-5 M to 3x10-3 M was called the "higher NE dose component". D 600 (3x10-8 M …