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Effect of sympathectomy on inotropic responsiveness to alpha-adrenoceptor stimulation in developing mouse myocardia
H Tanaka1, T Matsuda, M Adachi
1Department of Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Abstract:
Effects of postnatal sympathectomy on inotropic responsiveness to alpha-adrenoceptor stimulation were examined in mouse myocardia to determine whether the developmental conversion of alpha-adrenoceptor-mediated inotropic responses from positive to negative is triggered by sympathetic innervation. Sympathectomy was performed chemically by consecutively administering 6-hydroxydopamine for 14 days after birth and confirmed by the absence of inotropic responses to tyramine. In newborn myocardia, phenylephrine, in the presence of propranolol, produced concentration-dependent positive inotropic responses. Three weeks after birth, phenylephrine, in the presence of propranolol, produced concentration-dependent negative inotropic responses, both in control and in sympathectomized myocardia; no difference was observed between the two groups of mice in the maximum decrease in contractile force produced by phenylephrine. The sensitivity (pD2 value) to phenylephrine was significantly higher in sympathectomized myocardia. In conclusion, sympathetic innervation of the mouse ventricular myocardium is not required for the developmental conversion of the alpha-adrenoceptor-mediated inotropic response from positive to negative.
Insights
Sympathetic innervation is not required for the developmental shift in mouse heart muscle alpha-adrenoceptor responses from positive to negative inotropy. This finding impacts understanding of cardiac autonomic regulation.
Area of Science:
- Cardiovascular Physiology
- Developmental Biology
- Neuropharmacology
Background:
- Alpha-adrenoceptors in the heart change function during development.
- Sympathetic innervation plays a key role in cardiac regulation.
Purpose of the Study:
- To investigate if sympathetic innervation triggers the developmental switch in alpha-adrenoceptor inotropic responses.
- To understand the role of sympathetic innervation in cardiac development.
Main Methods:
- Postnatal chemical sympathectomy using 6-hydroxydopamine in mice.
- Assessment of inotropic responses to phenylephrine (alpha-adrenoceptor agonist) with propranolol (beta-blocker).
- Confirmation of sympathectomy via absence of tyramine response.
Main Results:
- Newborn mouse hearts showed positive inotropic responses to phenylephrine.
- Adult control and sympathectomized hearts exhibited negative inotropic responses to phenylephrine.
- No significant difference in the magnitude of negative inotropy between control and sympathectomized groups.
- Increased sensitivity to phenylephrine in sympathectomized hearts.
Conclusions:
- Sympathetic innervation is not essential for the developmental conversion of alpha-adrenoceptor inotropic responses from positive to negative.
- The developmental switch in cardiac alpha-adrenoceptor function occurs independently of sympathetic innervation.