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Metoclopramide (10 mg i.v. injection followed by 10 mg/h i.v. for 2 h) caused a transient rise in blood concentrations of aldosterone in sodium-replete and sodium-depleted sheep. Infusion of metoclopramide into the adrenal artery of sheep with an autotransplanted adrenal gland, at a rate to give a similar concentration of metoclopramide at the adrenal cell level (calculated from rate of infusion and adrenal blood flow), resulted in no alteration in aldosterone secretion rate in either sodium-replete or sodium-depleted animals, even though intravenous metoclopramide caused transient stimulation of aldosterone secretion in the same sheep when sodium replete.

Dopamine administered either into the adrenal arterial blood supply or intravenously had no significant effect on aldosterone secretion and did not reverse the stimulatory effects of angiotensin II on aldosterone secretion in the adrenal transplant.

The data do not support the suggestion that direct dopaminergic elements play a tonic inhibitory role in aldosterone secretion. It is possible that the agonist effect of metoclopramide on aldosterone secretion may occur by some non-dopaminergic mechanism and it is tempting to speculate that the effect is centrally mediated.

SUMMARY

The effect of sodium depletion on the conversion of corticosterone to aldosterone has been examined in vivo using the adrenal transplants of two sheep. [³H]Corticosterone was infused continuously directly into the adrenal gland via the carotid artery over a period of 30 min. and the total adrenal effluent was collected via the jugular vein in six consecutive 5-min. samples. The conversion of [³H]corticosterone to [³H]aldosterone and the endogenous output of aldosterone was measured in each sample using a double isotope derivative method and the specific activity of the aldosterone calculated. Radioactive conversion of B → aldosterone reached equilibrium within 10 min. of the start of infusion and remained constant over a period of 10–25 min. Aldosterone secretion was also constant during the first 25 min. of infusion.

In the same sheep the mean percentage conversion increased as aldosterone secretion rose over a range of 2–12 μg./hr. With more severe sodium depletion, i.e. with aldosterone secretion rates of 12–16 μg./hr., conversion decreased to that found in the sodium replete state. The specific activity of the aldosterone was constant throughout the mildly deplete range (2–12 μg./hr.) but fell with severe sodium depletion. In the sodium replete range (0–2 μg./hr.) before the introduction of a parotid fistula, the specific activity was the same as in the mildly deplete state. After the introduction of a parotid fistula the specific activity increased as the secretion decreased from 2 to 0 μg.

The validity of the approach and interpretation of the results in terms of the biosynthetic pathways involved are discussed.