Chronic adriamycin treatment and its effect on the cardiac beta-adrenergic system in the rabbit
Détails
ID Serval
serval:BIB_62587AAECF97
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Chronic adriamycin treatment and its effect on the cardiac beta-adrenergic system in the rabbit
Périodique
Journal of Cardiovascular Pharmacology
ISSN
0160-2446 (Print)
Statut éditorial
Publié
Date de publication
05/1992
Volume
19
Numéro
5
Pages
770-8
Notes
In Vitro
Journal Article --- Old month value: May
Journal Article --- Old month value: May
Résumé
Treatment of male rabbits with adriamycin at a cardiotoxic dose (1 mg/kg intravenously, i.v., twice a week for 9 weeks) caused cardiovascular disturbances characteristic of chronic heart failure. The severity of symptoms varied, indicating differences in the individual sensitivity of the animals to adriamycin. Thus, cardiac output (CO) was decreased by greater than 40% in only 4 of the 7 animals in which it was measurable at 9 weeks. Elevated levels of atrial natriuretic factor (ANF) and plasma renin activity (PRA), as well as pulmonary congestion, hydrothorax, and ascites were also evident. The baroreflex response to sodium nitroprusside (NPS) was blunted. The response to the inotropic drug dobutamine was depressed by 50% as compared with the control animals. Right ventricular beta-adrenoceptor density was significantly reduced in these animals (22.9 +/- 3.1 as compared with 31.8 +/- 1.0 fmol/mg protein in control animals) owing to a selective downregulation of the beta 1-adrenoceptor population. The loss of beta-adrenoceptors was highly correlated with severity of heart failure symptoms: i.e., baroreflex dysfunction as indicated by the NPS slope (r = 0.91), decrease in CO during the previous weeks (r = 0.88), and plasma norepinephrine (NE) levels (r = 0.96). However, when all adriamycin-treated animals were compared collectively regardless of the severity of heart failure, with the controls, no difference in the beta-adrenoceptor density was detectable, a finding in agreement with previous observations in this model. Chronic treatment of rabbits with adriamycin thus causes low-output failure, reflecting some of the findings reported for the human disease; however, individual sensitivity to adriamycin varies considerably between rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)
Mots-clé
Animals
Atrial Natriuretic Factor/blood
Blood Pressure/drug effects
Cardiac Output/*drug effects
Cardiac Output, Low/*chemically induced
Dobutamine/diagnostic use
Down-Regulation
Doxorubicin/administration & dosage/*pharmacology
Heart/*drug effects
Heart Rate/drug effects
Injections, Intravenous
Male
Nitroprusside/pharmacology
Organ Size/drug effects
Pressoreceptors/drug effects
Rabbits
Receptors, Adrenergic, beta/*drug effects
Renin/blood
Pubmed
Web of science
Création de la notice
05/03/2008 17:41
Dernière modification de la notice
20/08/2019 15:19