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Beta-adrenoceptor density in chronic infarcted myocardium: a subtype specific decrease of beta1-adrenoceptor density
R L Anthonio1, O E Brodde, D J van Veldhuisen
1Department of Clinical Pharmacology, University of Groningen, The Netherlands.
Insights
In chronic myocardial infarction, total beta-adrenoceptor density decreases significantly. This reduction is specifically due to a decrease in beta1-adrenoceptor density, not beta2-adrenoceptor density.
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
- Pharmacology
Background:
- Beta-adrenoceptor density is known to change in various cardiac conditions, being downregulated in heart failure and upregulated in acute ischemia.
- In the acute phase post-myocardial infarction, total beta-adrenoceptor density is reduced.
Purpose of the Study:
- To determine if total beta-adrenoceptor number is altered in the chronic phase following myocardial infarction.
- To investigate the specificity of these alterations, examining both beta1- and beta2-adrenoceptor subtypes.
Main Methods:
- Male Wistar rats underwent coronary artery ligation or a sham operation.
- Twelve weeks post-operation, hearts were analyzed for total beta-adrenoceptor number and the relative densities of beta1- and beta2-adrenoceptors in infarcted and non-infarcted myocardium.
Main Results:
- Total beta-adrenoceptor number was significantly decreased in infarcted myocardium compared to sham and non-infarcted myocardium.
- This decrease was attributed to a significant reduction in beta1-adrenoceptor density.
- Beta2-adrenoceptor density and dissociation constant remained unchanged.
Conclusions:
- In the chronic phase after myocardial infarction, total beta-adrenoceptor density is reduced in the infarcted myocardium.
- The observed decrease in total beta-adrenoceptor density is primarily due to a significant downregulation of beta1-adrenoceptor density.
Unlabelled:
Beta-adrenoceptor density is altered in different cardiac diseases. In heart failure beta-adrenoceptor density is down regulated but in acute myocardial ischemia beta-adrenoceptor density is up regulated. In hearts with myocardial infarction total beta-adrenoceptor density is decreased shortly after myocardial infarction.
Aims And Methods:
To investigate whether total beta-adrenoceptor number is altered in the chronic phase after myocardial infarction, and to identify the specificity of alteration, we studied male Wistar rats (n = 18) which underwent a ligation of the left coronary artery or a sham operation. Twelve weeks after coronary ligation, rats were sacrificed and hearts were excised, perfused to obtain blood-free myocardium and frozen in liquid nitrogen. Infarcted myocardium was identified visually and separated from non-infarcted myocardium. Total beta-adrenoceptor number was calculated in fmol (-)-[125I]iodocyanopindolol specifically bound/mg protein and the relative amount of beta1- and beta2-adrenoceptor density was measured by inhibition of (-)-[125I]iodocyanopindolol binding with CGP 20712 A.
Results:
Total beta-adrenoceptor number in infarcted myocardium was significantly decreased (25.7+/-1.4 vs. 24.9+/-2.2 vs. 20.1+/-3.2 fmol/mg protein (P=0.03) resp. Sham vs. Non-infarcted vs. Infarcted myocardium), due to a decrease of only beta1-adrenoceptor density (14.7+/-0.61 vs. 12.7+/-1.09 vs. 4.84+/-0.96 fmol/mg protein (P=0.004) resp.), whereas the beta2-adrenoceptor density and the dissociation constant (Kd) were not significantly decreased.
Conclusion:
In the infarcted myocardium total beta-adrenoceptor density is decreased due to a decreased beta1-adrenoceptor density at 12 weeks after myocardial infarction.