J. R. Womble

Adrenal medulla denervation prevents stress-induced epinephrine plasma elevation and cardiac hypertrophy.

Abstract Circulating catecholamines have been proposed as trophic agents for the heart. Denervation of the adrenal medullae, the major source of plasma epinephrine, totally blocked left ventricular hypertrophy after aortic coarctation in the dog. The level of epinephrine after adrenal medullary cholinergic denervation dropped to a mean of 10 pg/ml within 48 hours compared to 317 pg/ml in coarcted dogs with intact adrenal innervation, and 116 pg/ml in sham-coarcted controls. Decreased epinephrine levels were concomitant with a decrease in the heart weight to body weight ratios. These data implicate epinephrine as the specific hormone regulating cardiac hypertrophy.

Epinephrine elevation in plasma parallels canine cardiac hypertrophy.

Abstract Increased circulating epinephrine levels paralled cardiac hypertrophy in response to aortic constriction in the dog. Venous levels of epinephrine were significantly elevated at 24, 48, 72 and 96 hours postcoarctation. There were not significant arterial or venous alterations in norepinephrine levels. Dogs administered propranolol daily had no detectable hypertrophy 96 hours postcoarctation. We suggest that an increased epinephrine level may contribute to the physiological trigger(s) for cardiac hypertrophy.

Transglutaminase may mediate certain physiological effects of endogenous amines and of amine-containing therapeutic agents

Transglutaminase mediation of the effects of certain primary amines and alcohols may be important in receptor coupling to physiological responses. Many of the therapeutic and toxic side effects of drugs also may be related to their covalent linkage of glutamine residues of key regulatory proteins through the catalytic action of transglutaminase. This paper suggests that important therapeutic agents such as digoxin, tetracycline, adriamycin, and actinomycin D may have some effects related to transglutaminase action.

β2-ADRENOCEPTORS REGULATE INDUCTION OF MYOCARDIAL ORNITHINE DECARBOXYLASE IN MICE in vivo

1 The pharmacological characteristics of the myocardial adrenoceptor of the mouse have been examined during embryogenesis by measuring ornithine decarboxylase (ODC, EC 4.1.1.17) induction. 2 A four fold elevation of ODC activity was observed after isoprenaline (10 mg/kg, s.c), and enzyme activity was increased two to three fold following adrenaline (1 mg/kg, s.c.) or terbutaline given by direct injection to the foetus (10 μg/500 mg). 3 Pretreatment with the β‐adrenoceptor antagonist, propranolol (10 mg/kg), totally blocked the increase in ODC activity. 4 Elevation of myocardial ODC activity was not inhibited by metoprolol, a relatively specific β1‐adrenoceptor antagonist, at a dose of 10 mg/kg. 5 Since the increase in ODC activity was blocked by a β‐adrenoceptor antagonist (propranolol) and enzyme activity was stimulated by terbutaline, a β2‐agonist, we conclude that β2‐adrenoceptors are selectively coupled to the regulation of murine cardiac ODC activity following catecholamine stimulation.

A model of delayed aortic coarctation employing arterial and venous catheters for chronic blood sampling in conscious dogs.

We have developed a reproducible model of cardiac hypertrophy in conscious, unrestrained dogs after recovery from surgical trauma. The model has many potential applications due to the availability of non-stressful blood sampling from four arterial and/or venous vascular locations. Samples of blood for biochemical or pharmacological measurements were obtained from the carotid and femoral arteries as well as the pulmonary artery and inferior vena cava. Left ventricular hypertrophy up to 128% of the non-operated control animals was produced at 96 h post-intraluminal aortic coarctation. Inflation of a balloon in the descending aorta increased outflow resistance and resulted in hypertrophy. Hemodynamic parameters of cardiac function were obtained via a Swan-Ganz cardiac output catheter located permanently in the pulmonary artery. Complications observed in the dog model were minimal and mortality did not occur during the experimental period. This animal model employing multiple implanted catheters for blood sampling plus the ability to impose aortic coarctation in the unrestrained animal provides a flexible model system for biochemical and pharmacological research.