The positive inotropic and calcium-mobilizing effects of growth hormone-releasing peptides on rat heart.
GH-releasing peptides (GHRP) are synthetic peptides exerting GH-dependent or GH-independent effects via GH secretagogue receptor on many organs, including the heart. The underlying mechanisms of the cardiotropic properties of GHRP are poorly understood. This study investigates these effects of four GHRP in isolated perfused heart preparations and isolated neonatal and adult ventricular myocytes. The calcium response of cardiocytes to GHRP was visualized using confocal microscopy. All tested GHRP facilitated both ventricular contraction and relaxation in a dose-dependent manner, moderately decreasing coronary flow, but not modifying heart rate. GHRP induced a biphasic increase in intracellular free Ca2+ of the cardiocytes, consisting of a transient phase (phase 1), followed by a plateau phase (phase 2). Phase 1 was abolished by pretreatment with thapsigargin, a Ca2+-adenosine triphosphatase inhibitor of the sarcoplasmic reticulum. The phase 2 response was eliminated by removing extracellular free Ca2+, by verapamil, a voltage-gated Ca2+ channel blocker, or by 24-h pretreatment with phorbol 12-myristate 13-acetate, down-regulating protein kinase C. In isolated (denervated) heart, GHRP have a direct cardiotropic, without chronotropic, effect. GHRP elevate myocardial intracellular free Ca2+ through activating Ca2+ influx via voltage-gated Ca2+ channels and triggering Ca2+ release from thapsigargin-sensitive intracellular Ca2+ stores. Protein kinase C mediates the GHRP-induced Ca2+ influx, but not Ca2+ release. These finding support a number of roles for GHRP in the cardiovascular system.
Xu
Xiang-Bin
XB
Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Sciences, School of Basic Medicine, Peking Union Memorial College, Beijing 10005, China.
Cao
Ji-Min
JM
Pang
Jing-Jiang
JJ
Xu
Rong-Kun
RK
Ni
Chao
C
Zhu
Wen-Ling
WL
Asotra
Kamlesh
K
Chen
Meng-Chin
MC
Chen
Chen
C
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003326:Coronary Circulation / Q000187:drug effects; D013007:Growth Hormone-Releasing Hormone / Q000737:chemistry / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000254:growth & development; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D010446:Peptide Fragments; D019344:Lactic Acid; D019289:Pyruvic Acid; D013007:Growth Hormone-Releasing Hormone; D002118:Calcium