Date of Award
Doctor of Philosophy
The development of cardiac hypertrophy and other changes were examined during sub-chronic ethanol intoxication in Sprague-Dawley rats. Several experimental manipulations were evaluated: adrenal medullectomy, peripheral sympathectomy and the administration of adrenergic antagonists, prazosin and metoprolol. Ethanol, given by gavage every eight hours for up to 96 hours, maintained the rats in an ataxic state. It was found that adrenal cortical tissue hypertrophied after ethanol exposure. The release of adrenal medullary catecholamines was stimulated, producing a decline in contents, particularly of adrenaline, which was reflected in elevations in urinary catecholamines. Cardiac noradrenaline levels were reduced. These changes were paralleled by cardiac hypertrophy which reached 20 percent after 96 hours of intoxication.;Adrenal medullectomy attenuated the development of cardiomegaly. A small degree of hypertrophy did occur after 96 hours as did slight increases in urinary noradrenaline of extra-adrenal origin. Ethanol treatment after peripheral, non-adrenal sympathectomy, using 6-hydroxydopamine, provoked a greater cardiotrophic response from treatment-induced cardiac supersensitivity. Treatment with ethanol and prazosin augmented adrenal catecholamine release and the development of hypertrophy and reduced cardiac noradrenaline contents by more than 70 percent. Beta adrenoceptor blockade with metoprolol completely abolished the cardiotrophic response. Metoprolol treatment of control animals induced a slight regression of heart size. Estimations of catecholamine turnover rates in various peripheral tissues revealed that the adrenal medulla was virtually selectively stimulated.;The cardiotrophic response correlated directly with the excretion of urinary catecholamines. Peripheral sympathectomy provoked a parallel shift of the cardiotrophic response curve to the left, indicating increased sensitivity, whereas metoprolol shifted it to the right, reflecting decreased responsivity to catecholaminergic stimulation. Prazosin did not produce a shift in this curve. Taken together, these results suggest a strong association between the development of cardiac hypertrophy during sub-chronic ethanol intoxication and stimulation of cardiac beta-1 adrenergic receptors by catecholamines predominantly of adrenal medullary origin. A number of clinical implications are presented.
Adams, Michael Anthony, "The Development Of Cardiac Hypertrophy During Sub-chronic Ethanol Intoxication: The Role Of Adrenal Medullary Catecholamines" (1985). Digitized Theses. 1444.