http://www.cnr.it/ontology/cnr/individuo/prodotto/ID23500
Amiodarone inhibits the 3,5,3''-triiodothyronine-dependent increase of sodium/potassium adenosine triphosphatase activity and concentration in human atrial myocardial tissue (Articolo in rivista)
- Type
- Label
- Amiodarone inhibits the 3,5,3''-triiodothyronine-dependent increase of sodium/potassium adenosine triphosphatase activity and concentration in human atrial myocardial tissue (Articolo in rivista) (literal)
- Anno
- 2004-01-01T00:00:00+01:00 (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
- 10.1089/1050725041517084 (literal)
- Alternative label
Forini F., Nicolini G., Balzan S., Ratto G.M., Murzi B., Vanini V., Iervasi G (2004)
Amiodarone inhibits the 3,5,3''-triiodothyronine-dependent increase of sodium/potassium adenosine triphosphatase activity and concentration in human atrial myocardial tissue
in Thyroid (N.Y.N.Y.); Mary Ann Liebert Inc., New Rochelle (Stati Uniti d'America)
(literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- Forini F., Nicolini G., Balzan S., Ratto G.M., Murzi B., Vanini V., Iervasi G (literal)
- Pagina inizio
- Pagina fine
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
- Rivista
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
- Note
- ISI Web of Science (WOS) (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
- CNR-IFC, Pisa;
CNR Institute of Neurophysiology Pisa, Italy.
Pasquinucci Hospital, Division of Cardio surgery, CNR, Massa, Italy. (literal)
- Titolo
- Amiodarone inhibits the 3,5,3''-triiodothyronine-dependent increase of sodium/potassium adenosine triphosphatase activity and concentration in human atrial myocardial tissue (literal)
- Abstract
- In animal models the function of the sodium pump (sodium/potassium-adenosine triphosphatase [Na /K -
ATPase]) is enhanced by 3,5,3 -triiodothyronine (T3) and inhibited by the antiarrhythmic agent amiodarone.
However, it is still unclear whether the effect of the drug on Na /K -ATPase depends on the interference with
thyroid hormone action. We evaluated the interaction of T3 with amiodarone on Na /K -ATPase activity and
site number in human myocardium. Right atrial slices were cultured with (T3
) and without (T3
) 3 nM T3 in
presence and absence of amiodarone at therapeutical dose (1.5 M). When compared to T3
, T3
preparations
showed decreased 3H-ouabain binding (p 0.004) and lower 20-minute and 45-minute 86Rb-uptake (p 0.004).
Amiodarone caused an average 49% reduction of the T3
-dependent 3H-ouabain binding and decreased the
Western blot signal for the Na /K -ATPase 1 subunit. The drug also inhibited T3-dependent increase in 86Rbinflux
at 20 and 45 minutes by 66% and 42%, respectively, without affecting the affinity of the pump for K .
No differences were found in the 3H-ouabain binding and 86Rb-uptake of T3
, T3
amio and T3
amiodarone.
In conclusion, T3 stimulates the Na /K -ATPase in human atrial myocardium by increasing the number of
ouabain-binding sites, whereas amiodarone decreases the sodium pump function secondarily to the antagonism
with thyroid hormone.
491
Introduction
THYROID HORMONES ARE KNOWN TO influence cardiac contractile
and electrical activity. A possible mechanism for
these effects might involve the control of sodium/potassiumadenosine
triphosphatase (Na /K -ATPase), the key determinant
of the plasma membrane electrochemical gradient (1).
Indeed, several studies in animal models have suggested that
the sodium pump units are regulated by the thyroid status (1).
Low concentrations of the (Na /K -ATPase are associated
with hypothyroidism, and the treatment of hypothyroid animals
with the biologically active 3,5,3 -triiodothyronine (T3)
increases Na /K -ATPase activity by directly upregulating
the Na /K -ATPase gene expression (2,3).
The sodium pump units are also influenced by the antiarrhythmic
compound amiodarone. In the animal heart
long-term treatment with the drug reduces Na /K -ATPase
activity (4,5). The antiarrhythmic action of amiodarone involves
use-dependent block of Na , Ca2 , and K channels
(6). At the same time, because of its structural similarities to
thyroid hormones, the drug is believed to cause in the heart
several features that are characteristic of hypothyroidism
(7,8). Amiodarone, or its active metabolite desethylamiodarone
likely inhibits peripheral conversion of thyroxine (T4)
to T3 and antagonizes the binding of T3 to its nuclear receptors
(9-12). However, it is unclear whether, at least in part,
amiodarone exerts its pharmacological effects by interfering
with the action of thyroid hormone; the data regarding this
issue are controversial (13,14). Moreover the regulatory effect
of T3 on the sodium pump in the human heart is not as
clear nor are the interactions of amiodarone and thyroid system
on Na /K -ATPase function. Therefore, the aim of this
study was to assess the influence of treatment with T3
and/or amiodarone on Na /K -ATPase activity and number
of sodium pump sites in an ex vivo human myocardial
model. (literal)
- Editore
- Prodotto di
- Autore CNR
- Insieme di parole chiave
Incoming links:
- Prodotto
- Autore CNR di
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi
- Editore di
- Insieme di parole chiave di