Clonidine evokes vasodepressor responses via alpha(2)-adrenergic receptorsin gigantocellular reticular formation

The gigantocellular depressor area (GiDA) is a functionally defined subdivi sion of the medullary gigantocellular reticular formation where vasodepress or responses are evoked by glutamate nanoinjections. The GiDA also contains reticulospinal neurons that contain the alpha(2A)-adrenergic receptor (alp ha(2A)-AR). In the present study, we sought to determine whether nanoinject ions of the alpha(2)-AR agonist clonidine into the GiDA evoke cardiovascula r responses and whether these responses can be attributed to the alpha(2)-A R. We found that nanoinjections of clonidine into the GiDA evoke dose-depen dent decreases in arterial pressure and heart rate. These responses were eq uivalent in magnitude to responses produced by clonidine nanoinjections int o the sympathoexcitatory region of the rostral ventrolateral medulla. Furth ermore, the vasodepressor and bradycardic responses produced by clonidine i njections into the GiDA were blocked in a dose-dependent fashion by the hig hly selective alpha(2)-AR antagonist 2-methoxyidazoxan, but not by prazosin , which is an antagonist at both the alpha(1)-AR and the 2B subtype of the alpha-AR. The antagonism by 2-methoxyidazoxan was site specific because inj ections of the antagonist into the rostral ventrolateral medulla failed to block the responses evoked by clonidine injections into the GiDA. These fin dings support the notion that clonidine produces sympathoinhibition through multiple sites within the medullary reticular formation, which is consiste nt with the wide distribution of the alpha(2)-AR in reticulospinal neurons. These data also suggest that clonidine may have multiple mechanisms of act ion because it evokes a cardiovascular depressive response from regions con taining neurons that have been determined to be both sympathoinhibitory and sympathoexcitatory.