Cardiovascular effects of intravenous ghrelin infusion in healthy young men

American Journal of Physiology - Heart and Circulatory Physiology

Volumn 293, Issue 5, 2007, Pages

  Vestergaard, Esben Thyssen ^a   Andersen, Niels Holmark ^a   Hansen, Troels Krarup ^a   Rasmussen, Lars Melholt ^a   Moller, Niels ^a   Sorensen, Keld E ^a   Sloth, Erik ^a   Jorgensen, Jens Otto Lunde ^a  

^a AARHUS UNIVERSITY HOSPITAL   (Denmark)

Author keywords

Endothelium dependent flow mediated vasodilatation; Left ventricular function; Tissue Doppler imaging; Tissue tracking

Indexed keywords

CATECHOLAMINE; FATTY ACID; GHRELIN; GLUCOSE; GROWTH HORMONE; HYDROCORTISONE; PLACEBO;

ADULT; ARTICLE; CARDIOVASCULAR EFFECT; CATECHOLAMINE BLOOD LEVEL; CLINICAL TRIAL; CONTINUOUS INFUSION; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; FATTY ACID BLOOD LEVEL; GLUCOSE BLOOD LEVEL; GROWTH HORMONE BLOOD LEVEL; HEART LEFT VENTRICLE EJECTION FRACTION; HUMAN; HUMAN EXPERIMENT; HYDROCORTISONE BLOOD LEVEL; MALE; NORMAL HUMAN; PRIORITY JOURNAL; RANDOMIZATION; RANDOMIZED CONTROLLED TRIAL; VASODILATATION; VOLUNTEER;

ADULT; BLOOD FLOW VELOCITY; BLOOD PRESSURE; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; GHRELIN; HUMANS; INFUSIONS, INTRAVENOUS; MALE; REFERENCE VALUES; STROKE VOLUME; VASODILATION;

EID: 36148983403     PISSN: 03636135     EISSN: 15221539     Source Type: Journal    
DOI: 10.1152/ajpheart.00496.2007     Document Type: Article

References (52)

1. Abraham TP, Nishimura RA. Myocardial strain: can we finally measure contractility? J Am Coll Cardiol 37: 731-734, 2001.
2. Alvarez-Castro P, Isidro ML, Garcia-Buela J, Dieguez C, Casanueva FF, Cordido F. Effect of acute ghrelin administration on glycaemia and insulin levels in obese patients. Diabetes Obes Metab 8: 555-560, 2006.
3. Andersen NH, Poulsen SH. Evaluation of the longitudinal contraction of the left ventricle in normal subjects by Doppler tissue tracking and strain rate. J Am Soc Echocardiogr 16: 716-723, 2003.
4. Andersen NH, Terkelsen CJ, Sloth E, Poulsen SH. Influence of preload alterations on parameters of systolic left ventricular long-axis function: a Doppler tissue study. J Am Soc Echocardiogr 17: 941-947, 2004.
5. Baldanzi G, Filigheddu N, Cutrupi S, Catapano F, Bonissoni S, Fubini A, Malan D, Baj G, Granata R, Broglio F, Papotti M, Surico N, Bussolino F, Isgaard J, Deghenghi R, Sinigaglia F, Prat M, Muccioli G, Ghigo E, Graziani A. Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT. J Cell Biol 159: 1029-1037, 2002.
6. Barazzoni R, Bosutti A, Stebel M, Cattin MR, Roder E, Visintin L, Cattin L, Biolo G, Zanetti M, Guarnieri G. Ghrelin regulates mitochondrial-lipid metabolism gene expression and tissue fat distribution in liver and skeletal muscle. Am J Physiol Endocrinol Metab 288: E228-E235, 2005.
7. Bisi G, Podio V, Valetto MR, Broglio F, Bertuccio G, Aimaretti G, Pelosi E, Del Rio G, Muccioli G, Ong H, Boghen MF, Deghenghi R, Ghigo E. Cardiac effects of hexarelin in hypopituitary adults. Eur J Pharmacol 381: 31-38, 1999.
8. Broglio F, Benso A, Valetto MR, Gottero C, Quaranta L, Podio V, Arvat E, Bobbio M, Bisi G, Ghigo E. Growth hormone-independent cardiotropic activities of growth hormone-releasing peptides in normal subjects, in patients with growth hormone deficiency, and in patients with idiopathic or ischemic dilated cardiomyopathy. Endocrine 14: 105-108, 2001.
9. Brook R, Grau M, Kehrer C, Dellegrottaglie S, Khan B, Rajagopalan S. Intrasubject variability of radial artery flow-mediated dilatation in healthy subjects and implications for use in prospective clinical trials. Am J Cardiol 96: 1345-1348, 2005.
10. Camina JP. Cell biology of the ghrelin receptor. J Neuroendocrinol 18: 65-76, 2006.
11. Chang L, Ren Y, Liu X, Li WG, Yang J, Geng B, Weintraub NL, Tang C. Protective effects of ghrelin on ischemia/reperfusion injury in the isolated rat heart. J Cardiovasc Pharmacol 43: 165-170, 2004.
12. Chang L, Zhao J, Li GZ, Geng B, Pan CS, Qi YF, Tang CS. Ghrelin protects myocardium from isoproterenol-induced injury in rats. Acta Pharmacol Sin 25: 1131-1137, 2004.
13. Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D, Vallance P, Vita J, Vogel R. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 39: 257-265, 2002.
14. Enomoto M, Nagaya N, Uematsu M, Okumura H, Nakagawa E, Ono F, Hosoda H, Oya H, Kojima M, Kanmatsuse K, Kangawa K. Cardiovascular and hormonal effects of subcutaneous administration of ghrelin, a novel growth hormone-releasing peptide, in healthy humans. Clin Sci (Lond) 105: 431-435, 2003.
15. Eriksson BM, Persson BA. Determination of catecholamines in rat heart tissue and plasma samples by liquid chromatography with electrochemical detection. J Chromatogr 228: 143-154, 1982.
16. Espelund U, Hansen TK, Hojlund K, Beck-Nielsen H, Clausen JT, Hansen BS, Orskov H, Jorgensen JO, Frystyk J. Fasting unmasks a strong inverse association between ghrelin and cortisol in serum: studies in obese and normal-weight subjects. J Clin Endocrinol Metab 90: 741-746, 2005.
17. Frascarelli S, Ghelardoni S, Ronca-Testoni S, Zucchi R. Effect of ghrelin and synthetic growth hormone secretagogues in normal and ischemic rat heart. Basic Res Cardiol 98: 401-405, 2003.
18. Gnanapavan S, Kola B, Bustin SA, Morris DG, McGee P, Fairclough P, Bhattacharya S, Carpenter R, Grossman AB, Korbonits M. The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab 87: 2988-2991, 2002.
19. Hansen TK, Dall R, Hosoda H, Kojima M, Kangawa K, Christiansen JS, Jorgensen JO. Weight loss increases circulating levels of ghrelin in human obesity. Clin Endocrinol (Oxf) 56: 203-206, 2002.
20. Hornig B, Arakawa N, Kohler C, Drexler H. Vitamin C improves endothelial function of conduit arteries in patients with chronic heart failure. Circulation 97: 363-368, 1998.
21. Iglesias MJ, Pineiro R, Blanco M, Gallego R, Dieguez C, Gualillo O, Gonzalez-Juanatey JR, Lago F. Growth hormone releasing peptide (ghrelin) is synthesized and secreted by cardiomyocytes. Cardiovasc Res 62: 481-488, 2004.
22. Janssen JA, Poldermans D, Hofland LJ, Vourvouri EC, Muller AF, Bax JJ, Deghenghi R, Broglio F, Ghigo E, Van der Lely AJ. There are no acute cardiac effects of a single iv dose of human ghrelin in severe growth hormone deficient patients. J Endocrinol Invest 27: 659-664, 2004.
23. 125I- His(9)]-ghrelin, a novel radioligand for localizing GHS orphan receptors in human and rat tissue: up-regulation of receptors with atherosclerosis. Br J Pharmacol 134: 143-149, 2001.
24. Kim WY, Sogaard P, Egeblad H, Andersen NT, Kristensen B. Three-dimensional echocardiography with tissue harmonic imaging shows excellent reproducibility in assessment of left ventricular volumes. J Am Soc Echocardiogr 14: 612-617, 2001.
25. Kim WY, Sogaard P, Egeblad H, Andersen NT, Kristensen B. Three-dimensional echocardiography with tissue harmonic imaging shows excellent reproducibility in assessment of left ventricular volumes. J Am Soc Echocardiogr 14: 612-617, 2001.
26. Kinugawa S, Tsutsui H, Ide T, Nakamura R, Arimura K, Egashira K, Takeshita A. Positive inotropic effect of insulin-like growth factor-1 on normal and failing cardiac myocytes. Cardiovasc Res 43: 157-164, 1999.
27. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402: 656-660, 1999.
28. Kola B, Hubina E, Tucci SA, Kirkham TC, Garcia EA, Mitchell SE, Williams LM, Hawley SA, Hardie DG, Grossman AB, Korbonits M. Cannabinoids and ghrelin have both central and peripheral metabolic and cardiac effects via AMP-activated protein kinase. J Biol Chem 280: 25196-25201, 2005.
29. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise J, Solomon S, Spencer KT, St John SM, Stewart W. Recommendations for chamber quantification. Eur J Echocardiogr 7: 79-108, 2006.
30. Locatelli V, Rossoni G, Schweiger F, Torsello A, De Gennaro CV, Bernareggi M, Deghenghi R, Muller EE, Berti F. Growth hormone-independent cardioprotective effects of hexarelin in the rat. Endocrinology 140: 4024-4031, 1999.
31. Lucidi P, Murdolo G, Di Loreto C, Parlanti N, De Cicco A, Fatone C, Taglioni C, Fanelli C, Broglio F, Ghigo E, Bolli GB, Santeusanio F, De Feo P. Metabolic and endocrine effects of physiological increments in plasma ghrelin concentrations. Nutr Metab Cardiovasc Dis 15: 410-417, 2005.
32. McLaughlin T, Abbasi F, Lamendola C, Frayo RS, Cummings DE. Plasma ghrelin concentrations are decreased in insulin-resistant obese adults relative to equally obese insulin-sensitive controls. J Clin Endocrinol Metab 89: 1630-1635, 2004.
33. Nagaya N, Kojima M, Uematsu M, Yamagishi M, Hosoda H, Oya H, Hayashi Y, Kangawa K. Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. Am J Physiol Regul Integr Comp Physiol 280: R1483-R1487, 2001.
34. Nagaya N, Miyatake K, Uematsu M, Oya H, Shimizu W, Hosoda H, Kojima M, Nakanishi N, Mori H, Kangawa K. Hemodynamic, renal, and hormonal effects of ghrelin infusion in patients with chronic heart failure. J Clin Endocrinol Metab 86: 5854-5859, 2001.
35. Nagaya N, Moriya J, Yasumura Y, Uematsu M, Ono F, Shimizu W, Ueno K, Kitakaze M, Miyatake K, Kangawa K. Effects of ghrelin administration on left ventricular function, exercise capacity, and muscle wasting in patients with chronic heart failure. Circulation 110: 3674-3679, 2004.
36. Okumura H, Nagaya N, Enomoto M, Nakagawa E, Oya H, Kangawa K. Vasodilatory effect of ghrelin, an endogenous peptide from the stomach. J Cardiovasc Pharmacol 39: 779-783, 2002.
37. Pan C, Hoffmann R, Kuhl H, Severin E, Franke A, Hanrath P. Tissue tracking allows rapid and accurate visual evaluation of left ventricular function. Eur J Echocardiogr 2: 197-202, 2001.
38. Papotti M, Ghe C, Cassoni P, Catapano F, Deghenghi R, Ghigo E, Muccioli G. Growth hormone secretagogue binding sites in peripheral human tissues. J Clin Endocrinol Metab 85: 3803-3807, 2000.
39. Sasso FC, Carbonara O, Cozzolino D, Rambaldi P, Mansi L, Torella D, Gentile S, Turco S, Torella R, Salvatore T. Effects of insulin-glucose infusion on left ventricular function at rest and during dynamic exercise in healthy subjects and noninsulin dependent diabetic patients: a radionuclide ventriculographic study. J Am Coll Cardiol 36: 219-226, 2000.
40. Shimizu Y, Nagaya N, Teranishi Y, Imazu M, Yamamoto H, Shokawa T, Kangawa K, Kohno N, Yoshizumi M. Ghrelin improves endothelial dysfunction through growth hormone-independent mechanisms in rats. Biochem Biophys Res Commun 310: 830-835, 2003.
41. Takaya K, Ariyasu H, Kanamoto N, Iwakura H, Yoshimoto A, Harada M, Mori K, Komatsu Y, Usui T, Shimatsu A, Ogawa Y, Hosoda K, Akamizu T, Kojima M, Kangawa K, Nakao K. Ghrelin strongly stimulates growth hormone release in humans. J Clin Endocrinol Metab 85: 4908-4911, 2000.
42. Tesauro M, Schinzari F, Iantorno M, Rizza S, Melina D, Lauro D, Cardillo C. Ghrelin improves endothelial function in patients with metabolic syndrome. Circulation 112: 2986-2992, 2005.
43. Tesfamariam B, Cohen RA. Free radicals mediate endothelial cell dysfunction caused by elevated glucose. Am J Physiol Heart Circ Physiol 263: H221-H226, 1992.
44. Tschop M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature 407: 908-913, 2000.
45. Vestergaard ET, Hansen TK, Gormsen LC, Jakobsen P, Moller N, Christiansen JS, Jorgensen JO. Constant intravenous ghrelin infusion in healthy young men: clinical pharmacokinetics and metabolic effects. Am J Physiol Endocrinol Metab 292: E1829-E1836, 2007.
46. Vitale C, Mercuro G, Cornoldi A, Fini M, Volterrani M, Rosano GM. Metformin improves endothelial function in patients with metabolic syndrome. J Intern Med 258: 250-256, 2005.
47. Volterrani M, Desenzani P, Lorusso R, d'Aloia A, Manelli F, Giustina A. Haemodynamic effects of intravenous growth hormone in congestive heart failure. Lancet 349: 1067-1068, 1997.
48. Waggoner AD, Bierig SM. Tissue Doppler imaging: a useful echocardiographic method for the cardiac sonographer to assess systolic and diastolic ventricular function. J Am Soc Echocardiogr 14: 1143-1152, 2001.
49. Wiggers H, Norrelund H, Nielsen SS, Andersen NH, Nielsen-Kudsk JE, Christiansen JS, Nielsen TT, Moller N, Botker HE. Influence of insulin and free fatty acids on contractile function in patients with chronically stunned and hibernating myocardium. Am J Physiol Heart Circ Physiol 289: H938-H946, 2005.
50. Wiley KE, Davenport AP. Comparison of vasodilators in human internal mammary artery: ghrelin is a potent physiological antagonist of endothelin-1. Br J Pharmacol 136: 1146-1152, 2002.
51. Wilmshurst P. Growth hormone in end-stage heart failure. Lancet 349: 1842-1843, 1997.
52. Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, Dhillo WS, Ghatei MA, Bloom SR. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 86: 5992-5995, 2001.