CARDIOVASCULAR-RESPONSES TO AGMATINE, A CLONIDINE-DISPLACING SUBSTANCE, IN ANESTHETIZED RAT

We investigated the cardiovascular responses in anesthetized ventilate d rats to agmatine (decarboxylated arginine), an amine which is an end ogenous clonidine-displacing substance (CDS) synthesized in brain. Int racisternal agmatine dose-dependently increased sympathetic nerve acti vity and arterial pressure (at 400 nmol by 8.7+/-2.1 mu V and 28.6+/-2 .7 mmHg, respectively) and blocked arterial baroreflex reflexes. Micro injection of agmatine into the rostral ventrolateral medulla (RVL) had no effect on arterial pressure or sympathetic nerve activity while io ntophoresis 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 sy mpathetic ganglia and by direct dilation of vascular smooth muscles. D espite binding like clonidine to alpha(2)-adrenergic receptors and imi dazoline (I)-receptors of both classes, agmatine does not replicate th e 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 famil y of molecules.