We investigated the cardiovascular responses in anesthetized ventilated rats to agmatine (decarboxylated arginine), an amine which is an endogenous clonidine-displacing substance (CDS) synthesized in brain. Intracisternal agmatine dose-dependently increased sympathetic nerve activity and arterial pressure (at 400 nmol by 8.7 +/- 2.1 microV and 28.6 +/- 2.7 mmHg, respectively) and blocked arterial baroreflex reflexes. Microinjection of agmatine into the rostral ventrolateral medulla (RVL) had no effect on arterial pressure or sympathetic nerve activity while iontophoresis of agmatine onto defined vasomotor neurons of RVL was also without effect. Agmatine (i.v.) decreased sympathetic nerve activity and arterial pressure probably by blocking the transmission through sympathetic ganglia and by direct dilation of vascular smooth muscles. Despite binding like clonidine to alpha 2-adrenergic receptors and imidazoline (I)-receptors of both classes, agmatine does not replicate the central or peripheral actions of clonidine. The results suggest that earlier cardiovascular actions of partially purified CDS were either attributable to contaminating molecules and/or that CDS may be a family of molecules.