An isolated rabbit aortic preparation, on which drugs selectively act from the intimal surface was made. The contractile response of the aortic preparation to norepinephrine (NE) (1 nM-10 microM) administered from the intimal surface was considerably reduced by removal of the endothelium, whereas the response to KCl was not changed. The contractile response of the aortic preparation to electrical field stimulation (EFS) was abolished by the treatment with tetrodotoxin (1 microM), guanethidine (1 microM) or prazosin (10 microM), indicating that the response was elicited by the release of NE from the adrenergic nerve terminals. The contractile response of the aortic preparation to EFS was also considerably reduced by the removal of the endothelium. A nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine (100 microM) had almost no effect on the contractile response to EFS, indicating that the involvement of NO in the contractile response was negligible. In prostaglandin F2 alpha (PGF 2 alpha)-contracted aortic preparation, the contractile response to EFS was never converted into relaxing response by the treatment with prazosin (10 microM). The finding confirmed that adrenergic beta action of NE released from nerve terminals on the aorta was minor. These findings indicate that endogenously released NE from adrenergic nerve terminals as well as exogenously administered NE acts on the endothelium and may release endothelium derived contracting factor(s) which act together with NE on the vascular smooth muscle.