Microdialysis of noradrenaline in rostral ventrolateral medulla after intravenous methionine enkephalin administration in anesthetized rats

Abstract

The objective of this research was to define the role of central and peripheral opioid receptors for the regulation of cardiovascular action. Cardiovascular effects of methionine-enkephalin (met-enkephalin) after intracisternal, intravenous or direct administration into the rostral ventrolateral medulla (C1 area) were compared in inactin-anesthetized Sprague-Dawley rats. A microdialysis probe was stereotaxically implanted in the C1 area to dialyze monoamines during intravenous administration of met-enkephalin. An intravenous injection of met-enkephalin decreased both arterial pressure and heart rate in a dose-dependent manner. There were no cardiovascular responses to intracisternal dosages of up to 10 micrograms/kg, but as little as 0.1 micrograms/kg met-enkephalin decreased arterial pressure and heart rate after a direct injection into the C1 area. Onset of the met-enkephalin effect was similar regardless of drug doses after intravenous administration; however, duration and magnitude of the peptide's action and time to peak effect were directly related to the dose. Intravenous infusion of 100 micrograms/kg/min met-enkephalin increased the extracellular concentration of noradrenaline in the C1 area. There was a differential blockade by naloxone of the hypotensive action of met-enkephalin after intravenous or C1 administration. This study suggests the importance of both central and peripheral sites(s) of met-enkephalin for its cardiovascular action. Additionally, the data suggest that the C1 area is a communication site between catecholamines and opioid peptides for cardiovascular regulation.