Effect of Aminoglutethimide on Norepinephrine Turnover in the Rat Heart 1

Abstract

Stimulation of adrenergic nerves results in an increased synthesis of norepinephrine (NE). This has been demonstrated by electrical stimulation of the rat salivary gland (1), rat heart (2), guinea–pig vas deferens (3), and the cat adrenal gland (4). In addition, synthesis of NE in organs such as the heart has been reported increased following exercise and exposure to cold (5).

Imms and Jones (6) showed that adrenal–ectomized rats excreted significantly elevated amounts of catecholamines in urine, suggesting an increased sympathetic nerve activity. These investigators also showed that adrenal–ectomized rats have lowered blood pressure and proposed that this lowered blood pressure might trigger a partially compensating increase in sympathetic nerve activity, which would then give rise to the observed increase in urinary catecholamines (7).

Subsequently, increases in NE synthesis in adrenalectomized animals have been demonstrated in the rat brain (8) and in the rat heart (9, 10). In substantial agreement with this hypothesis were the findings of Lands–berg and Axelrod (9) and Landsberg et al. (11) that hypophysectomy also resulted in increased synthesis of NE in the rat heart, thus implicating the adrenal cortex. Additional evidence implicating the adrenal cortex was the observation that adrenal steroids administered to adrenalectomized rats prevented the increase in NE turnover (10, 12).

It has also been reported that adrenal demedullectomy results in an increase in the turnover of NE in the heart (13, 14). These data would tend to suggest that: (a) removal of either the adrenal cortex or the adrenal medulla results in increased turnover, (b) removal of the adrenal medulla, not the cortex, is the cause of the increased turnover, or (c) adrenal demedullectomy might sufficiently compromise the functioning of the adrenal cortex so that in reality the increased NE turnover observed following demedullectomy might be due to adrenal cortical insufficiency.