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Titolo:
Review of evidence for a novel model of cocaine-induced cardiovascular toxicity
Autore:
Knuepfer, MM; Mueller, PJ;
Indirizzi:
St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, St Louis, MO 63104 USA St Louis Univ St Louis MO USA 63104 & Physiol Sci, St Louis, MO 63104 USA
Titolo Testata:
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
fascicolo: 3, volume: 63, anno: 1999,
pagine: 489 - 500
SICI:
0091-3057(199907)63:3<489:ROEFAN>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
CENTRAL-NERVOUS-SYSTEM; INDUCED VENTRICULAR-FIBRILLATION; CALCIUM-CHANNEL ANTAGONISTS; CARDIAC-OUTPUT RESPONSES; CONSCIOUS RATS; INTRAVENOUS COCAINE; CORONARY-ARTERY; EXTRACELLULAR DOPAMINE; NUCLEUS-ACCUMBENS; VASCULAR-RESPONSES;
Keywords:
cardiac output; systemic vascular resistance; hemodynamic response variability; cocaine-induced toxicity; drug abuse; behavioral stress; population differences;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
115
Recensione:
Indirizzi per estratti:
Indirizzo: Knuepfer, MM St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, 1402 S Grand Blvd, St Louis, MO 63104 USA St Louis Univ 1402 S Grand Blvd St LouisMO USA 63104 104 USA
Citazione:
M.M. Knuepfer e P.J. Mueller, "Review of evidence for a novel model of cocaine-induced cardiovascular toxicity", PHARM BIO B, 63(3), 1999, pp. 489-500

Abstract

Cocaine is known to produce life-threatening cardiovascular complications in some but not all individuals. This review considers the premise that an appropriate animal model for cocaine-induced cardiotoxicity should be characterized by varying sensitivity in the population to the deleterious effects of cocaine. We have studied such a model in which physiological, biochemical, and pathological sensitivity to cocaine varies in rats. Our studies have identified a subset of rats that respond to cocaine with a decrease in cardiac output and a substantial increase in systemic vascular resistance (named vascular responders). In contrast, another group, designated mixed responders, is characterized by a smaller increase in systemic vascular resistance and a small increase in cardiac output. We reported that vascular responders are more likely to develop hypertension and cardiomyopathies with repeated cocaine administration. Under chloralose anesthesia, vascular responders have more profound presser responses to cocaine and an initial brief spike in renal sympathetic nerve activity not usually noted in mixed responders. Vascular responders have higher resting and cocaine-induced dopamine turnover in the striatum. In addition, vascular responders have higher alpha-adrenergic vasoconstrictor tone, whereas mixed responders have higher adrenergic cardiac tone. The difference in cardiac output and systemic vascularresistance responses to cocaine in these two subsets of the population canbe prevented by L-type calcium channel, muscarinic, or alpha-adrenergic blockade. Similar hemodynamic response variability is noted with other psychoactive agents and with acute stress, suggesting that the response patterns are not unique to cocaine. We propose that individual hemodynamic response variability is dependent on differences in CNS responsiveness and correlated with the incidence of cardiovascular disease. (C) 1999 Elsevier Science Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/12/20 alle ore 10:49:39