Hemodynamic and hormonal effects of human ghrelin in healthy volunteers.
To investigate hemodynamic and hormonal effects of ghrelin, a novel growth hormone (GH)-releasing peptide, we gave six healthy men an intravenous bolus of human ghrelin (10 microg/kg) or placebo and vice versa 1-2 wk apart in a randomized fashion. Ghrelin elicited a marked increase in circulating GH (15-fold). The elevation of GH lasted longer than 60 min after the bolus injection. Injection of ghrelin significantly decreased mean arterial pressure (-12 mmHg, P < 0.05) without a significant change in heart rate (-4 beats/min, P = 0.39). Ghrelin significantly increased cardiac index (+16%, P < 0.05) and stroke volume index (+22%, P < 0.05). We also examined ghrelin receptor [GH secretagogues receptor (GHS-R)] gene expression in the aortas, the left ventricles, and the left atria of rats by RT-PCR. GHS-R mRNA was detectable in the rat aortas, left ventricles, and left atria, suggesting that ghrelin may cause cardiovascular effects through GH-independent mechanisms. In summary, human ghrelin elicited a potent, long-lasting GH release and had beneficial hemodynamic effects via reducing cardiac afterload and increasing cardiac output without an increase in heart rate.
Nagaya
N
N
Department of Internal Medicine, National Cardiovascular Center, Osaka 565 - 8565, Japan.
Kojima
M
M
Uematsu
M
M
Yamagishi
M
M
Hosoda
H
H
Oya
H
H
Hayashi
Y
Y
Kangawa
K
K
D000328:Adult; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D000242:Cyclic AMP / Q000097:blood; D006152:Cyclic GMP / Q000097:blood; D004837:Epinephrine / Q000097:blood; D054439:Ghrelin; D006325:Heart Atria; D006352:Heart Ventricles; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D006728:Hormones / Q000097:blood* / Q000378:metabolism; D019382:Human Growth Hormone / Q000502:physiology; D006801:Humans; D007275:Injections, Intravenous; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood; D036361:Peptide Hormones; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D010907:Pituitary Hormones / Q000097:blood; D010919:Placebos; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D054439:Ghrelin; D006728:Hormones; D036361:Peptide Hormones; D010455:Peptides; D010907:Pituitary Hormones; D010919:Placebos; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D000242:Cyclic AMP; D006152:Cyclic GMP; D009638:Norepinephrine; D004837:Epinephrine