Effect of digoxin on the somatotroph responsiveness to growth hormone-releasing hormone (GHRH) alone or combined with arginine in normal young volunteers.

BACKGROUND: The activity of the GH/IGF-I axis, known to play a major role in myocardial structure and function, has been reported to be altered in patients with chronic heart failure. AIM AND DESIGN OF THE STUDY: In order to evaluate the possibility that clinically used cardioactive drugs may exert neuroendocrine influences on somatotroph secretion, we studied the effects of pretreatment with enalapril (20 mg/day orally for 3 days), furosemide (20 mg i.v. as a bolus at -5 minutes) or digoxin (0.25 mg orally 4x/day for 3 days) on the GH response to growth hormone-releasing hormone (GHRH) (1.0 microg/ kg i.v. as a bolus at 0 minutes) in 12 healthy male adults (age [mean +/- SEM] 30.2 +/- 1.4 years; BMI 22.7 +/- 0.7 kg/ m2). In a subgroup of 8 subjects the same study was performed testing the GH response to GHRH + arginine (ARG; 0.5 g/kg i.v. from 0 to + 30 minutes). RESULTS The GH response to GHRH (1,304.1 +/- 248-5 microg/l/h) was not modified by enalapril (1,368.7 +/- 171.2 microg/l/h) or by furosemide (1,269.3 +/- 185.2 microg/l/h) but was significantly blunted by digoxin (613.6 +/- 73.2 microg/l/h, P < 0.05). On the other hand digoxin, enalapril and furosemide did not modify the GH response to GHRH +ARG. CONCLUSIONS: Digoxin, but not enalapril or furosemide, inhibits the GH response to GHRH in normal subjects. The blunting effect of digoxin on the GHRH-induced GH response is counteracted by arginine. These findings show that digoxin possesses an inhibitory effect on somatotroph secretion that may be mediated at the hypothalamic level.