Biphasic dose-response curves of norepinephrine in vascular smooth muscle

IN isolated rabbits arterial preparations obtained from various anatomical locations: ear, saphenous, renal and femoral, cumulative dose-response curves of norepinephrine [NE] were constructed and compared under basal conditions and after graded treatment with phenoxybenzamine [PBZ]. In PBZ treated segments, biphasic dose-response curves were obtained. The biphasic dose-response curves were characterized by that after attaining an apparent maximum and levelling off at NE concentrations of about 10-[5] M, a second ascend occured when higher concentrationsof NE were used [up to 3X 10-[3]M]. Qualitatively similar biphasic dose-response curves were not obtained when the dextro isomer of NE was used as the agonist. Therefore, indicating the stereospecifity of the phenomenon. The results support the possibility of the existance of more than one type of adrenergic receptors that are responsible for the mediation of NE contractions in vascular smooth muscle, thus one type is preferentially stimulated by low NE concentrations and the other one by high concentration