Catecholamine-induced cardiac hypertrophy in a denervated, hemodynamically non-stressed heart transplant.
Studies of stress-induced cardiac hypertrophy suggest that myocardial mass is regulated by the circulating level of epinephrine. The trophic effect is mediated by cardiac beta-adrenergic receptors, and in the murine, rat, and dog heart, specifically by beta 2-adrenergic receptors. The well-characterized functional effects of catecholamines on heart have obscured their role as myocardial trophic hormones. Therefore, we compared the effect of beta-adrenergic receptor stimulation on the myocardial mass of both a working innervated heart and an essentially nonworking denervated heterotopically transplanted heart in the same rat; in this model, the neural and stretch parameters are nonoperational in the transplanted heart. Ornithine decarboxylase (ODC), an enzyme elevated in a dose-dependent manner in heart by isoproterenol, was assayed in both hearts to determine the relationship between ODC activity and myocardial mass in response to isoproterenol administration in working, innervated heart compared to denervated, nonworking heart. In both recipient and donor heart, the myocardial mass paralleled the ability of an isoproterenol bolus to stimulate ODC in the respective heart. However, beta-adrenergic receptor activity in the donor heart was decreased 5 days after transplantation as assessed by the differential ability of a single dose of isoproterenol to stimulate ODC activity. Beta-receptor coupling to ODC activity in the donor heart exceeded that of the recipient heart at 10 days posttransplantation suggesting a time-dependent elevation of beta-adrenergic receptor activity in donor heart. At all times, alterations in myocardial mass paralleled beta-adrenoceptor activity as assessed by the ability of isoproterenol administration to elevate ODC activity. The results support the concept that myocardial mass is regulated by the level of circulating hormones, particularly epinephrine.
Larson
D F
DF
Copeland
J G
JG
Russell
D H
DH
D000818:Animals; D001835:Body Weight; D006332:Cardiomegaly / Q000209:etiology*; D002395:Catecholamines / Q000502:physiology*; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000294:innervation; D016027:Heart Transplantation; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000201:enzymology; D009929:Organ Size; D009955:Ornithine Decarboxylase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D002395:Catecholamines; D009955:Ornithine Decarboxylase; D007545:Isoproterenol