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.
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.
Broglio
F
F
Department of Internal Medicine, University of Turin, Italy.
Benso
A
A
Gottero
C
C
Vito
L D
LD
Granata
R
R
Arvat
E
E
Bobbio
M
M
Trevi
G
G
Ghigo
E
E
D000328:Adult; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology; D001120:Arginine / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003864:Depression, Chemical; D004077:Digoxin / Q000494:pharmacology*; D004232:Diuretics / Q000494:pharmacology; D004656:Enalapril / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D006801:Humans; D008297:Male; D018709:Statistics, Nonparametric
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002316:Cardiotonic Agents; D004232:Diuretics; D004656:Enalapril; D004077:Digoxin; D005665:Furosemide; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D001120:Arginine