We evaluated possible interactions between angiotensin II (AII) or angiotensin III (AIII) and the alpha-2 adrenoceptors of the nucleus reticularis gigantocellularis (NRGC) in the medulla oblongata that are involved in cardiovascular regulation and antinociception, as well as the angiotensin receptor subtypes involved, using Sprague-Dawley rats that were anesthetized with pentobarbital sodium. The efficacy of guanabenz, which acts on the alpha-2 adrenoceptors in the NRGC to elicit hypotension, bradycardia and antinociception, based on tail-flick responses to noxious thermal stimuli (50 degrees C), was used as our experimental index. Bilateral microinjection of AII or AIII into the NRGC, at equimolar doses (40 pmol) that did not alter base-line systemic arterial pressure, heart rate or tail-flick latency, significantly and site-specifically attenuated the cardiovascular suppression elicited by guanabenz (100 micrograms/kg i.v.). This attenuation was appreciably antagonized by coadministration of the AT2 receptor antagonist PD-123319 (1.6 nmol). Concomitant examination of tail-flick responses revealed discernible inhibition by AII (40 pmol), but potentiation by AIII (40 pmol), of guanabenz-induced antinociception. These differential modulating effects of AII and AIII were, however, antagonized by comicroinjection of losartan (1.6 nmol) into the bilateral NRGC. Our results suggest that both AII and AIII produced a reduction, via AT2 receptors, of the activity of alpha-2 adrenoceptors in the NRGC that are involved in central cardiovascular regulation. On the other hand, antinociception induced by activation of alpha-2 adrenoceptors in the NRGC was suppressed by AII and potentiated by AIII, although AT1 receptors may play a major role in both interactions.