ISSN:
1432-2013
Keywords:
Positive Inotropic Effect
;
Dibutyryl-3′,5′-AMP
;
Isolated Rat
;
Atria
;
[Ca]e
;
Adrenaline and Theophylline
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary 1. In isolated electrically driven (frequency 2 Hz) rat left atria the N6-2′-O-dibutyryl derivative of cyclic 3′,5′-AMP (DB-AMP; monosodium salt) produced a concentration-dependent and reversible positive inotropic effect. In normal Tyrode solution (1.8 mM Ca++, the threshold concentration was 5×10−5 M; the peak concentration (10−3 M) increased contractile force to 203% of control values. Negative inotropic responses were not observed in these experiments even with supramaximal DB-AMP concentrations (Fig. 1). 2. The positive inotropic effect of DB-AMP developed gradualy (Fig. 2). It began 0.3–7.7 min after addition of the drug and was maximal within 3.5–28.3 min (Tab. 2). Once established, the effect was prolonged and decreased only slightly within 60 min (Fig. 2). 3. The positive inotropic effect of DB-AMP was due to an increase in the rate of tension development. The time to peak tension and the duration of contraction remained unchanged (Tab. 3). 4. At high concentrations (10−3–5×10−3M) DB-AMP caused contractures in some experiments (Tab. 1). 5. The time course and the magnitude of the inotropic effects of DB-AMP were influenced by the [Ca]e. The increment in myocardial contractility caused by 10−3M DB-AMP developed faster at high than at low [Ca]e (Tab. 4; Fig. 5). On the other hand, the positive inotropic effect of 10−3M DB-AMP was most evident at normal (1.8 mM) and reduced (0.45; 0.9 mM) [Ca]e, less pronounced at 3.6 mM Ca++ and was insignificant at 7.2 mM Ca++ (Fig.3). 6. Sodium butyrate (10−4–10−2M) did not alter the contractile behaviour of isolated rat atria. 7. In isolated electrically driven (frequency 3 Hz) left guinea-pig atria no positive inotropic effects could be demonstrated with DB-AMP at concentrations up to 10−3M. It is concluded that the positive inotropic action of DB-AMP—at least in isolated rat atria—may resemble that of adrenaline or theophylline in some points, e.g. with regard to its dependence on the [Ca]e. But as no positive inotropic effect could be observed in guinea-pig atria and as the mechanism by which DB-AMP augments contractile force remains obscure, the results are not thought to necessarily support the view that the effects of adrenaline or theophylline on contractile behaviour of mammalian cardiac muscle occur via cyclic AMP.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00592683
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