The effect of a β-adrenoceptor agonist on the release of the components of the vascular renin-angiotensin system was examined in vitro. Isolated rat mesenteric arteries were perfused in an open system with Krebs-Ringer solution and released immunoreactive angiotensin II (ANG IIir) into the perfusate was directly determined using a Sep-Pak C-18 cartridge connected to the perfusion system. Renin activity in the concentrated perfusate was also determined. Isoproterenol (1 nM-1 μM) increased the release of ANG IIir in a dose-dependent manner. The increase in ANG IIir release during isoproterenol (1 μM) infusion was inhibited by propranolol (1 μM) or captopril (2 μM). Isopro-terenol-induced increment of ANG IIir release was blocked by the selective β2-adrenoceptor antagonist, ICI 118,551 (1 μM), but not by the selective β1-adrenoceptor antagonist, atenolol (1 μM). Renin activity in the perfusate was measurable, but did not increase in response to isoproterenol (1 μM) infusion. There was no significant difference in the response of ANG IIir release to isoproterenol between spontaneously hypertensive rats and Wistar-Kyoto rats. The present results indicate that locally generated ANG II is released by β2-adrenoceptor activation. The β-adrenoceptor agonist and the vascular renin-angiotensin system may play an important role for the regulation of peripheral vascular tone.