hexarelin and Flushing

Reduced cardiac mass and performances are present in GH deficiency and are counteracted by rhGH replacement. GH and IGF-I possess specific myocardial receptors and have been reported able to exert an acute inotropic effect. Synthetic GH secretagogues (GHS) possess specific pituitary and hypothalamic but even myocardial receptors. In 7 male volunteers, we studied cardiac performance by radionuclide angiocardiography after iv administration of rhGH or hexarelin (HEX), a peptidyl GHS. The administration of rhGH or HEX increased circulating GH levels to the same extent (AUC: 1594.6+/-88.1 vs 1739.3+/-262.2 microg/l/min for 90 min) while aldosterone and catecholamine levels did not change; HEX, but not rhGH, significantly increased cortisol levels. Left ventricular ejection fraction (LVEF), mean blood pressure (MBP) and heart rate (HR) were unaffected by rhGH (62.4+/-2.1 vs 62.1+/-2.3%, 90.6+/-3.4 vs 92.0+/-2.5 mm Hg, 62.3+/-1.8 vs 66.7+/-2.7 bpm). HEX increased LVEF (70.7+/-3.0 vs 64.0+/-1.5%, p<0.03) without significant changes in MBP and HR (92.8+/-4.7 vs 92.4+/-3.2 mm Hg, 63.1+/-2.1 vs 67.0+/-2.9 bpm). LVEF significantly raised at 15 min, peaked at 30 min and lasted up to 60 min after HEX. These findings suggest that in man, the acute administration of Hexarelin exerts a short-lasting, positive inotropic effect. This effect seems GH-independent and might be mediated by specific GHS myocardial receptors.

Topics: Adult; Aldosterone; Angiocardiography; Blood Pressure; Cardiovascular System; Epinephrine; Flushing; Heart Rate; Hemodynamics; Human Growth Hormone; Humans; Hydrocortisone; Male; Norepinephrine; Oligopeptides; Time Factors

Growth hormone (GH)-releasing peptides possess specific pituitary, hypothalamic, and myocardial receptors. Seven adult male patients with GH deficiency (GHD) (age, mean+/-S.E.M.: 42.0+/-4.0 year) were studied by equilibrium radionuclide angiocardiography after i.v. administration of hexarelin, a peptide GH secretagogue. Data for these patients were compared with those for nine adult male controls (37.0+/-2.7 year). The GH response to hexarelin was negligible in patients with GHD compared to control subjects (CS) (peak: 1.9+/-0.9 vs. 45.7+/-3.6 microg/l, P<0.001). Basal left ventricular ejection fraction (LVEF) in patients with GHD was lower than that in CS (50+/-1% vs. 63+/-2%, P<0.001). Hexarelin administration increased LVEF both in patients with GHD and in CS (peak: 57+/-2 vs. 70+/-2, respectively, P<0.05 vs. baseline) without changing catecholamine levels, mean blood pressure (MBP), or cardiac output in either group. In conclusion, the acute administration of hexarelin exerts a short-lasting positive inotropic effect in humans, probably GH-independent and mediated by specific myocardial receptors for GH secretagogues.

Topics: Adult; Flushing; Heart; Hemodynamics; Human Growth Hormone; Humans; Hypopituitarism; Insulin-Like Growth Factor I; Male; Middle Aged; Oligopeptides; Radionuclide Angiography

GHRP-2 (D-Ala-D-beta Nal-Trp-D-Phe-Lys-NH2) and Hexarelin (HEX) (His-D-2-methylTrp-Ala-Trp-DPhe-Lys-NH2) are synthetic, non-natural super-analogs of GHRP-6 endowed with potent stimulatory effect on GH secretion and slight stimulatory effect on PRL, ACTH and cortisol levels. Their GH-releasing activity ahs never been compared each other and their effects on PRL, ACTH and cortisol have never been compared with that of other stimuli. To clarify these points, in 6 normal young adults (22-27 yr) we studied the GH, PRL, ACTH and cortisol responses to 1 and 2 micrograms/kg i.v. GHRP-2 and HEX comparing them with that after 1 micrograms/kg i.v. GHRH and 400 micrograms i.v. TRH + 2 micrograms/kg i.v. hCRH. The Gh responses to 2 micrograms/kg i.v. GHRP-2 or HEX, compared with those to 1 microgram/kg GHRH, were also studied in 6 normal elderly subjects (66-73 yr). In young adults 1 microgram/kg i.v. GHRP-2 and HEX induced a similar, strong GH response, which was higher (p < 0.05) than that to GHRH. The administration of 2.0 micrograms/kg i.v. GHRP-2 and HEX again elicited a similar GH response, which was higher (p < 0.05) than that after the 1.0 microgram/kg dose. In elderly subjects, the GH those in young subjects. In young adults, the PRL responses to all doses of GHRP-2 or HEX were similar and lower (p < 0.01) responses were similar to those to hCRH. In conclusion, our results demonstrate that, in man, GHRP-2 and HEX have similar, 2 and HEX is not fully specific, as they induce similar increases in PRL, ACTH and cortisol levels. The PRL-releasing activity of GHRPs is lower than that of TRH while their ACTH/cortisol-releasing activity is similar to that of hCRH.

Topics: Adrenocorticotropic Hormone; Adult; Aged; Aging; Corticotropin-Releasing Hormone; Flushing; Growth Hormone-Releasing Hormone; Growth Substances; Human Growth Hormone; Humans; Hydrocortisone; Male; Oligopeptides; Pituitary Hormone-Releasing Hormones; Prolactin; Thyrotropin-Releasing Hormone