The aim of the present study was to determine the inhibitory potency of two selective angiotensin AT 1 receptor antagonists, eprosartan and candesartan, at the level of the sympathetic nerve terminal and the vascular smooth muscle. Male New Zealand White rabbits, weighing 2100-2550 g, were used. To study eprosartan and candesartan at the neuronal angiotensin AT 1 receptor, we investigated their influence on the angiotensin II-enhanced, electrical field stimulation-evoked sympathetic transmission in the rabbit isolated thoracic aorta in a noradrenaline spillover model. To study both antagonists at the vascular angiotensin AT 1 receptor, concentration-response curves for angiotensin II were constructed in the presence or absence of the two angiotensin AT 1 receptor antagonists. Angiotensin II (10 nM) caused a significant increase by 107+/-11.1% of the stimulation-evoked sympathetic outflow, which was concentration-dependently inhibited by both eprosartan (pIC 5 0 7.91+/-0.12) and candesartan (pIC 5 0 10.76+/-0.13). Angiotensin II (1 nM-0.3 μM) caused a concentration-dependent increase in contractile force (E m a x 20.62+/-2.24 mN, pD 2 8.16+/-0.04). Both eprosartan (pA 2 8.90+/-0.11, pIC 5 0 8.87+/-0.12 (10 nM angiotensin II)) and candesartan (pD 2 ' 10.80+/-0.13) counteracted the contractions evoked by cumulative concentrations of angiotensin II. Candesartan proved a more potent antagonist than eprosartan at both the pre- and postjunctional angiotensin AT 1 receptor. For eprosartan, vascular inhibitory concentrations were 10-fold lower than sympatho-inhibitory concentrations, whereas for candesartan, inhibitory concentrations at both sites were similar. The results may be explained by differences between the pre- and postjunctional angiotensin AT 1 receptor subtype.