Effects of chronic myocardial infarction on responsiveness to isoprenaline and the state of myocardial beta adrenoceptors in rats.
Responsiveness to catecholamines and alterations in myocardial beta adrenoceptors were determined in rats with chronic myocardial infarction. Myocardial infarction was produced by ligating the left main coronary artery. Three weeks after myocardial infarction, when left ventricular function was impaired, catecholamine responsiveness was determined by measuring the effects of isoprenaline in the conscious animal, the isolated perfused heart, the isolated right atria, and the right papillary muscles. The catecholamine content and the density and affinity of beta adrenergic receptors [( 3H]dihydroalprenolol binding) were determined in non-ischaemic myocardium (ventricular septum). In conscious rats isoprenaline induced the same tachycardia in the sham operated as in the rats with infarction, but it induced only a slight increase of myocardial contractility because of a high basal sympathetic tone. In isolated perfused hearts, right atria, and right papillary muscles isoprenaline increased contractile force and heart rate with the same EC50 in both groups. However, in the infarcted group the maximal increase of contractile force induced by isoprenaline was smaller because of mechanical limitation due to the infarction. The catecholamine content was decreased in non-ischaemic myocardium and beta adrenergic density was increased by 30% (p less than 0.02) without any change of affinity. Thus in rats chronic myocardial infarction does not change the responsiveness of the non-ischaemic myocardium to isoprenaline and is not associated with a downregulation of the beta adrenoceptors.
Clozel
J P
JP
Pharmaceutical Research Department, F Hoffmann-La Roche & Co Ltd, Basel, Switzerland.
Holck
M
M
Osterrieder
W
W
Burkard
W
W
Da Prada
M D
MD
D000818:Animals; D002908:Chronic Disease; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol; D009638:Norepinephrine