Methyldopa in Rats with Sinoarortic Denervation: A Dynamic and Kinetic Profile with Microdyalisis

pp 491-496

Abstract

The pharmacokinetics of methyldopa (MD) (50 mg/kg; i.p.)and the effects on the dopaminergic metabolism was studied in anesthetized sham operated (SO) or sinoaortic denervated (SAD) rats, by means of the microdialysis technique. A vascular shunt probe was inserted into the carotid artery and concentric probe was placed in the striatum. Levels of MD, homovanillic acid (HVA) and 3.4-dihydroxi-phenylacetic acid (DOPAC) were measured by high-pressure liquid chromatography coupled to electro-chemical detection (HPLC-EC). Peak concentrations of MD in arterial blood were similar in both groups of rats but the t112was 171.6 ± 53.0 min for SO rats (n= 4) and 28.3 ±8.1 min for SAD rats (n = 4, p < 0.05). Methyldopa levels were stable along the experiment in the control group(SO).Lower levels of MD and a quick decrease were seen in striatum of SAD rats. Homovanillic acid and DOPAC levels in the striatal dialysates of SAD rats were decreased in 20%and 25%, respectively, compared to baseline.In conclusion, employing a microdialysis technique, we found different kinetic profiles of MD in dialysates from arterial blood and striatum of SO and SAD rats, at a dose of MD that alters the striatal dopaminergic metabolism.