Beta-adrenoceptor density in chronic infarcted myocardium: a subtype specific decrease of beta1-adrenoceptor density.
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.


OBJECTIVE
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.


CONCLUSIONS
In the infarcted myocardium total beta-adrenoceptor density is decreased due to a decreased beta1-adrenoceptor density at 12 weeks after myocardial infarction.
Anthonio
R L
RL
Department of Clinical Pharmacology, University of Groningen, The Netherlands.
Brodde
O E
OE
van Veldhuisen
D J
DJ
Scholtens
E
E
Crijns
H J
HJ
van Gilst
W H
WH
D000818:Animals; D002908:Chronic Disease; D015536:Down-Regulation; D006439:Hemodynamics; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*
D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2