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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2004-2-11
pubmed:abstractText
We investigated the contribution of the sympathetic nervous system (SNS) in maintaining blood pressure during administration of carvedilol in rats with dilated cardiomyopathy, and examined whether SNS hyperactivity induced by high-dose carvedilol is related to severity of heart failure. The hypotensive effect of carvedilol in rats with heart failure (Group F) was not significantly different to that in rats without (Group N). However, enhancement of the plasma norepinephrine concentration during carvedilol administration in Group F was higher than in Group N. The constitutive plasma NE concentration in Group F (562 +/- 146 pg/ml) was significantly higher than in Group N (203 +/- 55 pg/ml) and there was a significant positive correlation between the heart weight to body weight ratio and the plasma norepinephrine concentration. Values for the maximal effect of the norepinephrine hypertensive effect during norepinephrine intravenous infusion (Emax) decreased, and plasma norepinephrine concentrations at half-maximal effect of the norepinephrine hypertensive effect (EC50) increased in Group F compared with Group N (20.8 +/- 6.1 and 28.6 +/- 2.2 mmHg, and 4.5 +/- 1.9 and 1.5 +/- 0.2 ng/ml, respectively). These results suggested that the number of receptors (Emax) and sensitivity (EC50) to the norepinephrine hypertensive effect decreased in Group F. Changes in these parameters in Group F corresponded with the results of a beta-adrenergic receptor binding assay using I-125 iodocyanopindolol (Bmax = 32 +/- 4 in Group F and 53 +/- 2 fmol/mg protein in Group N). These results showed that the SNS (presynaptic) activity increased and the SNS receptor sensitivity in the blood pressure regulation system decreased in heart failure. Therefore, high-dose carvedilol treatment should be used with caution to avoid worsening heart failure.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0160-2446
pubmed:author
pubmed:issnType
Print
pubmed:volume
42 Suppl 1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
S93-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:14871037-Animals, pubmed-meshheading:14871037-Blood Pressure, pubmed-meshheading:14871037-Body Weight, pubmed-meshheading:14871037-Carbazoles, pubmed-meshheading:14871037-Cardiomyopathy, Dilated, pubmed-meshheading:14871037-Dose-Response Relationship, Drug, pubmed-meshheading:14871037-Epinephrine, pubmed-meshheading:14871037-Heart, pubmed-meshheading:14871037-Heart Rate, pubmed-meshheading:14871037-Hypertension, pubmed-meshheading:14871037-Hypotension, pubmed-meshheading:14871037-Infusions, Intravenous, pubmed-meshheading:14871037-Iodine Radioisotopes, pubmed-meshheading:14871037-Male, pubmed-meshheading:14871037-Myocardium, pubmed-meshheading:14871037-Norepinephrine, pubmed-meshheading:14871037-Organ Size, pubmed-meshheading:14871037-Presynaptic Terminals, pubmed-meshheading:14871037-Propanolamines, pubmed-meshheading:14871037-Radioligand Assay, pubmed-meshheading:14871037-Rats, pubmed-meshheading:14871037-Rats, Inbred Lew, pubmed-meshheading:14871037-Receptors, Adrenergic, beta-1, pubmed-meshheading:14871037-Sympathetic Nervous System, pubmed-meshheading:14871037-Ventricular Pressure
pubmed:year
2003
pubmed:articleTitle
Contribution of sympathetic nervous system activity during administration of carvedilol in rats with dilated cardiomyopathy.
pubmed:affiliation
Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, Japan. watanabe@niigata-pharm.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't