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Myocardial adenosine A1-receptor sensitivity during juvenile and adult stages of maturation
Ist Teil von
American journal of physiology. Heart and circulatory physiology, 1998-02, Vol.274 (2), p.H627
Ort / Verlag
United States
Erscheinungsjahr
1998
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
Department of Physiology, University of Massachusetts Medical
School, Worcester, Massachusetts 01655-0127
In the heart,
endogenous adenosine attenuates the -adrenergic-elicited increase in
contractile performance via activation of adenosine
A 1 receptors. It has been recently
reported that this function of adenosine becomes more pronounced with
myocardial maturation. The purpose of the present study was to
determine whether mature hearts possess a greater sensitivity than
immature hearts to this antiadrenergic effect of adenosine. Isolated
perfused hearts or atria from immature (ca. 23 days) and mature (ca. 80 days) rats were stimulated with isoproterenol (Iso), a -adrenergic agonist, at 10 8 M and
concomitantly exposed to increasing concentrations of
2-chloroN 6 -cyclopentyladenosine
(CCPA), a highly selective and potent adenosine A 1 -receptor agonist, from
10 12 to
10 6 M. CCPA at
10 10 -10 6
M dose dependently reduced the Iso-elicited contractile response more
in immature than in mature hearts or atria. At
10 6 M, CCPA reduced the
Iso-elicited contractile response by 103% in immature hearts and by
55% in mature hearts. These effects of CCPA were attenuated by the
adenosine A 1 -receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine at
10 7 M. In additional
experiments, CCPA exhibited similar effectiveness in reducing the
spontaneous heart rate of immature and mature hearts, an effect also
mediated by activation of adenosine
A 1 receptors. Similar to CCPA, the
adenosine A 1 -receptor agonist R - N 6 -(2-phenylisopropyl)adenosine
reduced the Iso-elicited contractile response more in immature than in
mature hearts, albeit with less effectiveness than CCPA. In agreement
with these results, CCPA reduced Iso-elicited adenylyl cyclase activity
more in immature than in mature hearts. Overall, in contrast with our
original hypothesis, these results indicate that immature hearts
display greater sensitivity than mature hearts to the antiadrenergic
effect of adenosine A 1 -receptor
activation.
perfused heart; -adrenergic receptor; contractility; adenylyl
cyclase