Cardiovascular and hormonal effects of subcutaneous administration of ghrelin, a novel growth hormone-releasing peptide, in healthy humans.
Ghrelin is a novel GH (growth hormone)-releasing peptide isolated from the stomach. The cardiovascular and hormonal effects of the subcutaneous administration of ghrelin in humans remain unknown. Six healthy volunteers each received subcutaneous administration of three doses of ghrelin (1, 5 or 10 microg/kg) and placebo; the order of administration was randomized, and separate doses were given at least 24 h apart. The serum GH level dose-dependently increased from 0.5 +/- 0.4 to 3.6 +/- 2.1 ng/ml (1 microg/kg ghrelin; P=0.99 compared with baseline), 27.1 +/- 12.0 ng/ml (5 microg/kg; P<0.01 compared with baseline) and 45.4 +/- 12.8 ng/ml (10 microg/kg; P<0.01 compared with baseline) 30 min after ghrelin administration. Subcutaneous administration of ghrelin did not significantly alter circulating levels of corticotropin, cortisol, insulin-like growth factor-1, noradrenaline or adrenaline, although 10 microg/kg ghrelin slightly increased the prolactin level. No significant changes in heart rate or mean arterial pressure were observed. In contrast, the left ventricular ejection fraction, as assessed by echocardiography, increased dose-dependently from 63.5 +/- 0.6% to 65.1 +/- 0.9% (1 microg/kg ghrelin; P=0.97 compared with baseline), 69.6 +/- 1.3% (5 microg/kg; P<0.01 compared with baseline) and 71.5 +/- 0.9% (10 microg/kg; P<0.01 compared with baseline) 30 min after ghrelin administration. These haemodynamic and hormonal changes were still apparent 60 min after ghrelin injection. In conclusion, subcutaneous administration of ghrelin dose-dependently induced relatively specific GH release and enhanced cardiac performance in humans.
Enomoto
Mitsunobu
M
Department of Internal Medicine, National Cardiovascular Center, Osaka, Japan.
Nagaya
Noritoshi
N
Uematsu
Masaaki
M
Okumura
Hiroyuki
H
Nakagawa
Eiichiroh
E
Ono
Fumiaki
F
Hosoda
Hiroshi
H
Oya
Hideo
H
Kojima
Masayasu
M
Kanmatsuse
Katsuo
K
Kangawa
Kenji
K
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000704:Analysis of Variance; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D004837:Epinephrine / Q000097:blood; D054439:Ghrelin; D013006:Growth Hormone / Q000097:blood*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D009638:Norepinephrine / Q000097:blood; D036361:Peptide Hormones / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D011388:Prolactin / Q000097:blood*; D013318:Stroke Volume / Q000187:drug effects*
D054439:Ghrelin; D036361:Peptide Hormones; D007334:Insulin-Like Growth Factor I; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D013006:Growth Hormone; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine