Cardiovascular effects of centrally perfused clonidine.
Earlier work has indicated that the systemic cardiovascular actions of clonidine might be mediated by caudal brainstem centers, especially the nucleus of the solitary tract (NTS). This study sought to define the mode of clonidine action on the NTS more explicitly using the technique of push-pull perfusion on urethane-anesthetized rats. The NTS of stereotaxically mounted subjects was unilaterally perfused with an artificial cerebrospinal fluid at 25 microliter/min. Clonidine was added to the medium at concentrations of 5 to 500 microM, without interruption of flow, for test periods of 10 min. Systemic drug actions were expressed in terms of mean arterial pressure (MAP) and heart rate (HR), both of which were recorded continuously throughout the experiment. Decreases occurred in both MAP and HR following clonidine perfusion at all concentrations. However, the dose-effect relationship for the blood pressure response was dependent to some extent on control pressure. When this was considered as a variable, the drug-induced pressure effects were significantly dose-dependent. Control HR values were more stable than pressure and dose-related decreases following clonidine administration were highly significant. The clonidine concentrations investigated here were considerably lower than those previously studied by microinjection. The observed dose-related depression of MAP and HR under basal conditions may be related to specific alpha 2-adrenergic receptor activation of the NTS.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology; D010477:Perfusion; D011311:Pressoreceptors / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology
D011942:Receptors, Adrenergic, alpha; D003000:Clonidine