Effect of Angiotensin-Converting Enzyme Inhibition on Pituitary Hormone Responses to Insulin-Induced Hypoglycemia in Humans*

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Renin, angiotensin-II, and angiotensin-converting enzyme (ACE) have been found in the hypothalamus and pituitary in rats, and renin, angiotensinogen, and ACE have been found in human pituitary lactotrophs. To determine the physiological relevance of the renin-angiotensin system in the pituitary hormone response to stress in humans, we created significant inhibition of ACE by administering a clinically used dose (10 mg) of enalapril (E) 4 h before measuring the stress hormone responses to insulin-induced hypoglycemia. Eight fasting lean healthy males (aged 20-35 yr) were given either placebo (P) or E (10 mg, orally) in two studies separated by at least 5 days in a blinded study design. Glucose, ACTH, cortisol, PRL, and GH levels were measured before E or P and at 20-min intervals beginning 20 min before insulin administration. ACE levels were similar at baseline (E, 21.6 +/- 2.7; P, 22.4 +/- 2.4 mU/mL/min), but were significantly lower at the time of insulin injection with E treatment (E, 2.9 +/- 0.5; P, 20.9 +/- 2.5 mU/mL/min; P less than 0.001). The mean of the total area under the curve of PRL secretion was significantly lower for the E group (E, 3767.2 +/- 710.7; P, 4554.9 +/- 650.1 micrograms/L.min; P less than 0.05). Although the mean peak PRL levels were lower for the E group, this did not reach statistical significance (E, 53.0 +/- 9.7; P, 64.4 +/- 9.4 micrograms/L; 0.05 less than P less than 0.10). These differences in PRL responses appeared to be due primarily to substantial decreases in PRL responses with E in three of the eight subjects. No significant differences were found with ACTH, cortisol, or GH for basal levels, peak levels, or areas under the curve.