Document Detail


Pharmacokinetic and pharmacodynamic alterations of methyldopa in rats with aortic coarctation. A study using microdialysis.
MedLine Citation:
PMID:  11712868     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A pharmacokinetic-pharmacodynamic study of methyldopa (MD) was made in anesthetized sham operated (SO) and aortic coarctated (ACo) rats by using a vascular shunt probe for arterial microdialysis and simultaneous blood pressure recording. Anesthetized Wistar rats were used 7 days after aortic coarctation or sham operation. A vascular shunt probe was inserted into the carotid artery and a concentric probe was placed into the striatum or posterior hypothalamus. MD and 3,4-dihydroxyphenylacetic acid (DOPAC) were determined in the dialysates by HPLC-EC. MD (50 mg kg(-1)i.p.) induced an increase of heart rate in SO (Delta HR: 108 +/- 22 bpm, n= 6) and in ACo rats (Delta HR: 55 +/- 10 bpm, n= 6, P< 0.05, one way ANOVA). Moreover, MD also reduced the mean arterial pressure (MAP) of SO rats (Delta MAP: -10 +/- 4 mmHg, n= 6) and ACo animals (Delta MAP: -51 +/- 9 mmHg, n= 6, P< 0.05, one way ANOVA). Analysis of the arterial blood dialysates showed a lower half-life of MD in ACo rats (t(1/2): 1.5 +/- 0.3 h, n= 6, P< 0.05, 't' test) than in SO rats (t(1/2): 3.7 +/- 1.0 h, n= 6). A low accumulation and a fast decay of striatal MD levels were seen in ACo rats. However, peak levels of drug were greater in the hypothalamic dialysates of ACo rats than in SO animals samples. On the other hand, MD also induced an increase of DOPAC levels in the hypothalamic dialysates of ACo rats. In conclusion, the aortic coarctation modifies the pharmacokinetic and cardiovascular effect of MD in the rat. The action of this drug on dopaminergic neurotransmission is also altered in the ACo animals.
Authors:
C Höcht; J A Opezzo; S B Gorzalczany; R M Priano; G F Bramuglia; C A Taira
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pharmacological research : the official journal of the Italian Pharmacological Society     Volume:  44     ISSN:  1043-6618     ISO Abbreviation:  Pharmacol. Res.     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-11-19     Completed Date:  2002-03-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8907422     Medline TA:  Pharmacol Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  377-83     Citation Subset:  IM    
Copyright Information:
Copyright 2001 Academic Press.
Affiliation:
Department of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, (C1113AAD) Buenos Aires, Junín 956, Argentina. chocht@ffyb.uba.ar
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MeSH Terms
Descriptor/Qualifier:
3,4-Dihydroxyphenylacetic Acid / metabolism
Animals
Antihypertensive Agents / pharmacokinetics*,  pharmacology
Aortic Coarctation / metabolism*,  physiopathology
Blood Pressure / drug effects
Corpus Striatum / drug effects,  metabolism
Dialysis Solutions / pharmacokinetics
Hypothalamus / drug effects,  metabolism
Methyldopa / administration & dosage,  pharmacokinetics*,  pharmacology
Microdialysis* / methods
Rats
Rats, Wistar
Chemical
Reg. No./Substance:
0/Antihypertensive Agents; 0/Dialysis Solutions; 102-32-9/3,4-Dihydroxyphenylacetic Acid; 555-30-6/Methyldopa

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