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Chronotropic and inotropic effects of histamine in developing chick heart: differential mechanisms before and after
H Tanaka1, N Uesato, K Shigenobu
1Department of Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Insights
Histamine impacts developing chicken hearts, causing positive chronotropic and inotropic effects. Mechanisms differ: embryonic hearts use direct H2 receptor action, while hatched hearts rely on norepinephrine release from sympathetic nerves.
Area of Science:
- Cardiology
- Developmental Biology
- Pharmacology
Background:
- Histamine is a biogenic amine with diverse physiological roles.
- Its effects on cardiac function during embryonic development are not fully understood.
- Chicken embryos provide a valuable model for studying cardiac development.
Purpose of the Study:
- To investigate the chronotropic and inotropic effects of histamine on embryonic and hatched chicken hearts.
- To elucidate the underlying mechanisms of histamine's cardiac actions during development.
- To compare the pharmacological responses between embryonic and post-hatch stages.
Main Methods:
- Isolated atrial and ventricular preparations from embryonic and hatched chickens were used.
- Concentration-response curves for histamine were generated.
- The effects of various antagonists (H1, H2, H3, propranolol, beta-adrenoceptor antagonists) and inhibitors (isobutylmethylxanthine, reserpine, desipramine) were assessed.
Main Results:
- Histamine induced positive chronotropic and inotropic responses in both embryonic and hatched hearts.
- In embryonic hearts, responses were mediated via H2 receptors.
- In hatched hearts, responses involved norepinephrine release from sympathetic nerve terminals, distinct from direct histamine receptor action.
Conclusions:
- Exogenous histamine exerts positive chronotropic and inotropic effects on developing chicken hearts.
- The mechanisms mediating these effects are developmentally regulated, shifting from direct H2 receptor activation in embryos to norepinephrine release in hatched chicks.
Abstract:
Chronotropic and inotropic effects of histamine were examined in isolated atrial and ventricular preparations from embryonic and hatched chicken hearts. Histamine produced positive chronotropic and inotropic responses both in embryonic and hatched hearts. The responses to histamine in middle embryonic myocardia, which were observed in the micromolar range, were antagonized by H2 antagonists but not by H1, H3 antagonists and propranolol. Isobutyl-methylxantine, an inhibitor of phosphodiesterase, produced a leftward shift of the concentration-response curve for the chronotropic effect of histamine in the embryo. The responses to histamine in myocardia from hatched chicks, which were observed in the milimolar range, appeared concurrently with the responses to tyramine during development and were antagonized by beta adrenoceptor antagonists but not by any of the histamine antagonists. The positive inotropic response to histamine in hatched ventricular preparations were greatly attenuated by reserpine pretreatment or in the presence of desipramine. Thus, we demonstrated that exogenously applied histamine produces positive chronotropic and inotropic responses in developing chicken hearts and that the mechanisms are different between embryonic and hatched chicks: direct action on H2 receptors in the embryonic heart and release of norepinephrine from sympathetic nerve terminals in hatched hearts.