Kinetic and Dynamic Approaches to Methyldopa Action in Rats with Aortic Coarctation

pp 769-773

Abstract

Methyldopa (MD) is an antihypertensive drug of central action. The aim of this work was to performa kinetic-dynamic approach of MD in aortic coarctated (ACo)and sham operated (SO) rats employing the microdialysis technique. Animals were anesthetized with chlorates-urethane. A vascular shunt probe was inserted in the carotid artery Thirty μd dialysates were collected every 15 minutes, and levels of MD was measured by HPLC-EC. Mean blood pressure (MBP) and heart rate (HR) were calculated from blood pressure recordings. In conscious SO rats (n = 20) basal MBP and HR were 102±3 mm Hg and 357 ±6 bpm respectively and in ACo animals (n = 20) basal values were 162 ± 5 mm Hg (p< 0.05) and 384 ±23 bpm. In anesthetized rats, basal PAM and HR of SO animals (n = 16) were 57 ±1 mmHg and 342 ± 12 bpm respectively, and basal PAM and HR of ACo rats (n = 16) were 81 ± 4 mm Hg (p< 0.05) and 365 ± 12 bpm respectively. MD(50 mg/kg IP) induced a peak increase of HR in SO (AHR:108 ± 22 bpm, n = 6) and in ACo rats (55 ± 10 bpm, n = 6, p < 0.05 versus SO rats). Moreover, MD also reduced the MBP of SO rats (-10 ± 4 mm Hg) and ACo animals (-51 ± 9 mm Hg, p < 0.05). The t112ofMD in SO rats was 3.7 ± 1.0 hours with a maximum blood concentration, 8.8 ±1.5. tg/ml, at 26 minutes after the drug administration. In ACo rats, the t112ofMD was 1.5 ± 0.3 hours (p < 0.05) and maximum blood concentration was 4.3 ±1.7 μ.g/ml (p < 0.05). In conclusion, the aortic coarctated rats were more sensitive to the cardiovascular action of methyl-dopa than control animals and showed altered drug kinetic parameters.