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Titolo:
Pharmacokinetic and pharmacodynamic alterations of methyldopa in rats withaortic coarctation. A study using microdialysis
Autore:
Hocht, C; Opezzo, JAW; Gorzalczany, SB; Priano, RM; Bramuglia, GF; Taira, CA;
Indirizzi:
Univ Buenos Aires, Fac Pharm & Biochem, Dept Pharmacol, Buenos Aires, DF, Argentina Univ Buenos Aires Buenos Aires DF Argentina Buenos Aires, DF, Argentina
Titolo Testata:
PHARMACOLOGICAL RESEARCH
fascicolo: 5, volume: 44, anno: 2001,
pagine: 377 - 383
SICI:
1043-6618(200111)44:5<377:PAPAOM>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
SINOAORTIC-DENERVATED RATS; HEPATIC DRUG-METABOLISM; MODEL TRAUMATIC INJURY; DOPAMINE RELEASE; INVIVO; DIALYSIS;
Keywords:
aortic coarctation; pharmacokinetic; pharmacodynamic; arterial pressure; methyldopa; microdialysis; 'shunt' probe;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Hocht, C Univ Buenos Aires, Fac Pharm & Biochem, Dept Pharmacol, Junin 956,C1113AAD, Buenos Aires, DF, Argentina Univ Buenos Aires Junin 956,C1113AADBuenos Aires DF Argentina a
Citazione:
C. Hocht et al., "Pharmacokinetic and pharmacodynamic alterations of methyldopa in rats withaortic coarctation. A study using microdialysis", PHARMAC RES, 44(5), 2001, pp. 377-383

Abstract

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 determinedin 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 (DeltaHR: 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) thanin 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 levelsin the hypothalamic dialysates of ACo rats. In conclusion, the aortic coarctation modifies the pharmacokinetic and cardiovascular effect of MD in therat. The action of this drug on dopaminergic neurotransmission is also altered in the ACo animals. (C) 2001 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/09/20 alle ore 20:16:28