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Developmental increase in the inotropic and cyclic AMP response to isoproterenol in embryonic and newly hatched
K Nakazawa1, Y Kusuya, K Shigenobu
1Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Insights
Chick embryo and newly hatched chick ventricles show different sensitivities to isoproterenol. This difference in response, particularly in cyclic adenosine 3
Area of Science:
- Cardiovascular Physiology
- Developmental Biology
- Pharmacology
Background:
- Sympathetic innervation is crucial for cardiovascular regulation.
- Perinatal development involves significant changes in cardiac function and responsiveness.
- Understanding developmental changes in cardiac adrenergic signaling is key.
Purpose of the Study:
- To investigate the mechanism of altered isoproterenol sensitivity in chick ventricles during perinatal development.
- To compare cyclic adenosine 3',5'-monophosphate (cyclic AMP) levels and contractile responses between embryonic and hatched chicks.
Main Methods:
- Isolated ventricles from 15- to 20-day-old chick embryos and 0- to 3-day-old hatched chicks were used.
- Responses to isoproterenol, sotalol, and 3-isobutyl-1-methylxanthine (IBMX) were measured.
- Inotropic effects and cyclic AMP levels were assessed.
Main Results:
- Isoproterenol induced a positive inotropic effect in both embryonic and hatched chick ventricles, with higher sensitivity in hatched chicks.
- Hatched chick ventricles showed increased reactivity to isoproterenol in elevating cyclic AMP levels.
- IBMX also increased contractile force, with hatched chicks responding to lower doses.
Conclusions:
- Chick ventricles exhibit increased sensitivity to isoproterenol post-hatching.
- Enhanced cyclic AMP production in response to isoproterenol likely underlies the heightened sensitivity in hatched chicks.
- Developmental changes in cyclic AMP production mechanisms contribute to altered adrenergic responsiveness.
Abstract:
The cyclic adenosine 3',5'-monophosphate (cyclic AMP) levels of ventricles isolated from 15- to 20-day-old chick embryos and 0- to 3-day-old hatched chicks were compared to clarify the mechanism underlying the change in sensitivity to isoproterenol during perinatal developmental stages when the functional sympathetic innervation has been completely achieved. Isoproterenol produced a positive inotropic effect on ventricles isolated from both embryonic and hatched chicks, but the ventricles from the hatched chicks were more sensitive. At both developmental stages sotalol was an equipotent antagonist of isoproterenol. 3-Isobutyl-1-methylxanthine (IBMX) produced an increment in the contractile force of the ventricles at both stages, but the ventricles from the hatched chicks responded to lower doses of IBMX. The reactivity to isoproterenol in increasing cyclic AMP level was significantly higher in the hatched ventricles than in the embryonic ventricles. The results suggest that the different sensitivities to isoproterenol between embryonic and newly hatched chick ventricles may be due to some changes in the process for cyclic AMP production.