Aging: ouabain-sensitive /sup 86/Rb+ uptake rate and responsiveness to digoxin in rat left atrial muscle

Journal Article · Sun Jan 01 04:00:00 EST 1989 · J. Pharmacol. Exp. Ther.; (United States)

OSTI ID:6470427

Kennedy, R H; Seifen, E

Previous work in anesthetized rats has demonstrated that the sensitivity to cardiotoxic actions of cardiotonic steroids is increased in senescence, and studies in crude homogenates and partially purified membrane preparations have suggested that this altered responsiveness is related to an aging-associated reduction in the sarcolemmal content of Na,K-adenosine triphosphatase. This decrease in Na,K-adenosine triphosphatase could enhance the sensitivity to digitalis-like compounds by reducing the reserve capacity of the Na+-pump and thus the extent of digitalis-induced pump inhibition required before the onset of toxicity. Current experiments examined dose-dependent actions of digoxin in atrial muscle isolated from 3-, 12- and 24- to 25-month-old rats and determined if alterations in responsiveness correlated with changes in ouabain-sensitive 86Rb+ uptake rate, an estimate of Na+-pump activity. Atrial preparations from aged rats were more sensitive to the cardiotoxic actions of digoxin; however, the inotropic efficacy before the onset of toxicity was not affected by age. Both 1) the maximum attainable ouabain-sensitive 86Rb+ uptake rate and 2) the difference between maximum uptake rate and that monitored in preparations stimulated at 4.0 Hz decreased progressively with age. These results indicate that atrial muscle from aged rats is more sensitive to direct toxic effects of digoxin and suggest that this lower tolerance is mediated, at least in part, by a reduction in Na+-pump reserve capacity.

• Research Organization: Univ. of Arkansas for Medical Sciences, Little Rock (USA)
• OSTI ID: 6470427
• Journal Information: J. Pharmacol. Exp. Ther.; (United States), Journal Name: J. Pharmacol. Exp. Ther.; (United States) Vol. 248:1; ISSN JPETA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACID ANHYDRASES
AGE DEPENDENCE
ALKALI METAL COMPOUNDS
ALKALI METAL ISOTOPES
ANIMALS
ATP
ATP-ASE
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CARBOHYDRATES
CARDIAC GLYCOSIDES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CARDIOVASCULAR SYSTEM
DAYS LIVING RADIOISOTOPES
DIGITALIS GLYCOSIDES
DIGOXIN
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ENZYMES
GLYCOSIDES
HEART
HYDROLASES
IN VITRO
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
MINUTES LIVING RADIOISOTOPES
MUSCLES
MYOCARDIUM
NUCLEI
NUCLEOTIDES
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
OUABAIN
PHOSPHOHYDROLASES
RADIOISOTOPES
RATS
RODENTS
RUBIDIUM 86
RUBIDIUM ISOTOPES
SENSITIVITY
SODIUM COMPOUNDS
STROPHANTHINS
TOXICITY
TRACER TECHNIQUES
UPTAKE
VERTEBRATES