Clonidine evokes vasodepressor responses via alpha2-adrenergic receptors in gigantocellular reticular formation.
The gigantocellular depressor area (GiDA) is a functionally defined subdivision of the medullary gigantocellular reticular formation where vasodepressor responses are evoked by glutamate nanoinjections. The GiDA also contains reticulospinal neurons that contain the alpha2A-adrenergic receptor (alpha2A-AR). In the present study, we sought to determine whether nanoinjections of the alpha2-AR agonist clonidine into the GiDA evoke cardiovascular responses and whether these responses can be attributed to the alpha2-AR. We found that nanoinjections of clonidine into the GiDA evoke dose-dependent decreases in arterial pressure and heart rate. These responses were equivalent in magnitude to responses produced by clonidine nanoinjections into the sympathoexcitatory region of the rostral ventrolateral medulla. Furthermore, the vasodepressor and bradycardic responses produced by clonidine injections into the GiDA were blocked in a dose-dependent fashion by the highly selective alpha2-AR antagonist 2-methoxyidazoxan, but not by prazosin, which is an antagonist at both the alpha1-AR and the 2B subtype of the alpha-AR. The antagonism by 2-methoxyidazoxan was site specific because injections of the antagonist into the rostral ventrolateral medulla failed to block the responses evoked by clonidine injections into the GiDA. These findings support the notion that clonidine produces sympathoinhibition through multiple sites within the medullary reticular formation, which is consistent with the wide distribution of the alpha2A-AR in reticulospinal neurons. These data also suggest that clonidine may have multiple mechanisms of action because it evokes a cardiovascular depressive response from regions containing neurons that have been determined to be both sympathoinhibitory and sympathoexcitatory.
Aicher
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SA
Department of Neurology and Neuroscience, Division of Neurobiology, Cornell University Medical College, New York, New York, USA. saaicher@med.cornell.edu
Drake
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CT
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D019329:Idazoxan / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D008845:Microinjections; D009474:Neurons / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D011224:Prazosin / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012154:Reticular Formation / Q000033:anatomy & histology / Q000166:cytology / Q000187:drug effects*
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; C058525:2-methoxyidazoxan; D003000:Clonidine; D011224:Prazosin; D019329:Idazoxan